Shangdong Liang

Nanchang University, Nan-ch’ang-shih, Jiangxi Sheng, China

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Publications (40)81.21 Total impact

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    ABSTRACT: Neuropathic pain is a very common complication in diabetes mellitus (DM), and treatment for it is limited. As DM is becoming a global epidemic it is important to understand and treat this problem. The mechanisms of diabetic neuropathic pain are largely obscure. Recent studies have shown that glial cells are important for a variety of neuropathic pain types, and we investigated what are the changes that satellite glial cells (SGCs) in dorsal root ganglia undergo in a DM type 1 model, induced by streptozotocin (STZ) in mice and rats. We carried out immunohistochemical studies to learn about changes in the activation marker glial fibrillary acidic protein (GFAP) in SGCs. We found that after STZ-treatment the number of neurons surrounded with GFAP-positive SGCs in dorsal root ganglia increased 4-fold in mice and 5-fold in rats. Western blotting for GFAP, which was done only on rats because of the larger size of the ganglia, showed an increase of about 2-fold in STZ-treated rats, supporting the immunohistochemical results. These results indicate for the first time that SGCs are activated in rodent models of DM1. As SGC activation appears to contribute to chronic pain, these results suggest that SGCs may participate in the generation and maintenance of diabetic neuropathic pain, and can serve as a potential therapeutic target.
    Journal of Cellular and Molecular Medicine 10/2014; · 4.75 Impact Factor
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    ABSTRACT: P2X3 receptors in stellate ganglia (SG) and cervical dorsal root ganglia (DRG) neurons are involved in sympathoexcitatory reflex induced by myocardial ischemic damage. Puerarin, a major active ingredient extracted from the traditional Chinese plant medicine Ge-gen, has been widely used in treatment of myocardial and cerebral ischemia. The present study is aimed to observe the effects of puerarin on the signaling transmission mediated by P2X3 receptor in SG and DRG after myocardial ischemic damage. Our results showed that systolic blood pressure and heart rate increased, and the expression levels of P2X3 mRNA and protein in SG and DRG were up-regulated after myocardial ischemic damage. Puerarin reduced systolic blood pressure and heart rate, relieved pain and decreased up-regulated expression of P2X3 mRNA and protein in SG and DRG after myocardial ischemia. Puerarin inhibited the up-regulated ATP-activated currents in DRG neurons after myocardial ischemia. Thus, puerarin can relieve myocardial ischemic damage through blocking the P2X3 signaling transmission and then depressed the aggravated sympathoexcitatory reflex.
    Brain research bulletin 01/2014; · 2.18 Impact Factor
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    ABSTRACT: Adenosine triphosphate (ATP) plays an important role in signal transmission via acting on P2X receptors. P2X7 receptor is involved in pathophysiological changes of ischemic diseases. The PC12 cell line is a popular model system to study sympathetic neuronal function. In this study, the effects of P2X7 on the viability or [Ca2 +]i in PC12 cells after exposure to oxygen-glucose deprivation (OGD) were investigated. The results showed that the viability of PC12 cells was decreased under the condition of OGD. BzATP, a P2X7 agonist, decreased the viability, while P2X7 antiagonist oxATP or P2X7 siRNA reversed the viability of PC12 cells under the condition of OGD. The expression levels of P2X7 mRNA and protein in PC12 cells were up-regulated under the condition of OGD or BzATP treatment. The expression levels of P2X7 mRNA and protein were significantly decreased in OGD PC12 cells, which were pretreated with oxATP or P2X7 siRNA. It was also found that oxATP or P2X7 siRNA effectively suppressed the increase of [Ca2 +]i induced by OGD. P2X7 agonist ATP or BzATP enhanced the [Ca2 +]i rise induced by OGD in PC12 cells. The [Ca2 +]i peak induced by ATP or BzATP in OGD group was decreased by ERK inhibitor U0126. Therefore, P2X7 antagonists or P2X7 siRNA could depress the sympathetic neuronal damage induced by ischemia.
    Autonomic neuroscience: basic & clinical 01/2014; · 1.82 Impact Factor
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    ABSTRACT: Myocardial ischemia elicits a sympathoexcitatory response characterized by increase in blood pressure and sympathetic nerve activity. Puerarin, a major active ingredient extracted from the traditional Chinese plant medicine Ge-gen, has been widely used in treatment of myocardial and cerebral ischemia. However, little is known about the mechanism. Our study was aimed to explore the effect of puerarin on sympathoexcitatory response induced by myocardial ischemic injury and possible relationship with P2X3 receptor. Our results showed that puerarin alleviated systolic blood pressure and heart rate, and decreased the up-regulated of P2X3 mRNA and protein in SCG of myocardial ischemic rats. The amplitude of ATP-activated currents of SCG neurons was much larger in myocardial ischemic group than that in control group. Puerarin reduced ATP-activated currents in myocardial ischemic group and control group, and the inhibiting effects of puerarin in myocardial ischemic group were stronger than those in control group. Puerarin also significantly inhibited ATP-activated currents in HEK293 cells transfected with P2X3 receptor. These results suggest that puerarin can depress up-sympathoexcitatory response induced by myocardial ischemia via acting on P2X3 receptor in rat SCG to protect myocardium.
    Neurochemistry International 01/2014; · 2.66 Impact Factor
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    ABSTRACT: Leptin, an adipocytokine produced mainly by white adipose tissue, has a broad role in the regulation of neuronal functions. Accumulating evidence has revealed that leptin plays an important role in influencing neuropathic pain, shown recently by the finding that chronic administration of leptin induced thermal hyperalgesia and mechanical allodynia in naive rats. Chronic constriction sciatic nerve injury (CCI) is a well characterized model used for studying neuropathic pain. The present study was designed to investigate whether leptin plays a role in neuropathic pain in rats induced by CCI by examining particular pain behaviors. After sciatic nerve injury in rats, endogenous levels of leptin and leptin receptor (OB-Rb) were increased in a time dependent manner within the ipsilateral dorsal root ganglion (DRG). Intrathecal administration of leptin once daily for 6 days, beginning 7 days after CCI, alleviated neuropathic pain and decreased the expression of IL-6, TNFalpha, and the P2X2 and P2X3 receptors. Attenuation of endogenous OB-Rb in the DRG by intrathecal administration of OB-Rb antisense oligonucleotides did not change thermal hyperalgesia or mechanical allodynia induced by CCI. Our findings suggest that exogenous leptin can alleviate the chronic neuropathic pain caused by CCI. The leptin effect may be mediated by attenuated expression of IL-6, TNFalpha, and the P2X2 and P2X3 receptors in the DRG of CCI rats.
    Molecular Pain 12/2013; 9(1):65. · 3.77 Impact Factor
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    ABSTRACT: Myocardial ischemic injury activates cardiac sympathetic afferent fibers and elicits a sympathoexcitatory reflex by exciting sympathetic efferent action, with resultant augmentation of myocardial oxygen consumption, leading to a vicious cycle of exaggerating myocardial ischemia. P2X7 receptor participates in the neuronal functions and the neurological disorders. This study examined the role of P2X7 receptor of superior cervical ganglia (SCG) in sympathoexcitatory reflex. Our results showed that the expression of P2X7 receptor at both mRNA and protein in SCG was increased after myocardial ischemic injury. P2X7 receptor agonists at the same concentration activated much larger amplitudes of the currents in the SCG neurons of myocardial ischemic rats than those in control rats. P2X7 receptor antagonist (brilliant blue G, BBG) significantly inhibited P2X7 receptor agonist-activated currents in the SCG neurons. Excessive phosphorylation of MAPK ERK1/2 upon the activation of P2X7 receptor might be a mechanism mediating the signal transduction after myocardial ischemic injury. Therefore, the sensitized P2X7 receptor in SCG was involved in the nociceptive transmission of sympathoexcitatory reflex induced by myocardial ischemic injury.
    Neurochemistry International 06/2013; · 2.66 Impact Factor
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    ABSTRACT: P2X receptors participate in cardiovascular regulation and disease. After myocardial ischemic injury, sensory-sympathetic coupling between rat cervical DRG nerves and superior cervical ganglia (SCG) facilitated sympathoexcitatory action via P2X7 receptor. The results showed that after myocardial ischemic injury, the systolic blood pressure, heart rate, serum cardiac enzymes, IL-6, and TNF-α were increased, while the levels of P2X7 mRNA and protein in SCG were also upregulated. However, these alterations diminished after treatment of myocardial ischemic (MI) rats with the P2X7 antagonist oxATP. After siRNA P2X7 in MI rats, the systolic blood pressure, heart rate, serum cardiac enzymes, the expression levels of the satellite glial cell (SGC) or P2X7 were significantly lower than those in MI group. The phosphorylation of ERK 1/2 in SCG participated in the molecular mechanism of the sympathoexcitatory action induced by the myocardial ischemic injury. Retrograde tracing test revealed the sprouting of CGRP or SP sensory nerves (the markers of sensory afferent fibers) from DRG to SCG neurons. The upregulated P2X7 receptor promoted the activation of SGCs in SCG, resulting in the formation of sensory-sympathetic coupling which facilitated the sympathoexcitatory action. P2X7 antagonist oxATP could inhibit the activation of SGCs and interrupt the formation of sensory-sympathetic coupling in SCG after the myocardial ischemic injury. Our findings may benefit the treatment of coronary heart disease and other cardiovascular diseases.
    Purinergic Signalling 06/2013; · 2.64 Impact Factor
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    ABSTRACT: Purinergic signaling has been found to participate in the regulation of cardiovascular function. In this study, using a rat myocardial ischemic injury model, the sympathoexcitatory reflex mediated by P2X7 receptor via sensory-sympathetic coupling between cervical dorsal root ganglia (DRG) nerves and stellate ganglia (SG) nerves was explored. Our results showed that the systolic blood pressure, heart rate, serum cardiac enzymes concentrations, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) concentrations were increased, and the expression levels of P2X7 mRNA and protein in DRG and SG were up-regulated after myocardial ischemic injury. Administration of brilliant blue G (BBG), a selective P2X7 antagonist, decreased the elevation of systolic blood pressure, heart rate, serum cardiac enzyme, IL-6 and TNF-α, and inhibited the up-regulated expression of P2X7 mRNA and protein in DRG and SG after myocardial ischemic injury. Retrograde tracing test showed that there were calcitonin gene-related peptide sensory nerves and substance P sensory nerves sprouting from DRG to SG, which played an important role in the development of myocardial ischemic injury. The up-regulated P2X7 receptor expression levels on the surface membrane of satellite glial cells contributed to the activation of sensory-sympathetic coupling, which in turn facilitated the sympathoexcitatory reflex. BBG can inhibit the activation of satellite glial cells and interrupt the generation of sensory-sympathetic coupling in the cervical sympathetic ganglia after the myocardial ischemic injury. Taken together, these findings may provide a new therapeutic approach for treating coronary heart disease, hypertension and other cardiovascular diseases.
    Brain research bulletin 05/2013; · 2.18 Impact Factor
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    ABSTRACT: Diabetic neuropathy (DNP) is the most common chronic complication of diabetes. Elevated free fatty acids (FFAs) have been recently recognized as a major cause of nervous system damage in diabetes. P2X receptors play a primary role in regulation of neuronal interleukin (IL)-6 release, which is of paramount relevance to the functional changes of nerve system. The present study aimed to investigate the effects of high FFAs on the P2X7 expression and IL-6 release in PC12 cells. High FFAs induced P2X7 expression and IL-6 release significantly in PC12 cells. Moreover, high FFAs enhanced ATP or BzATP-induced Ca2+ signals in PC12 cells. Inhibition of P2X7 by transfection with P2X7-siRNA or co-culture with BBG (a specific P2X7 inhibitor) at high concentrations of FFAs decreased ATP or BzATP-promoted Ca2+ signals and IL-6 release in PC12 cells. High FFAs induced the phosphorylation of p38 in PC12 cells. Blockade of p38 pathways by SB-203580 inhibited P2X7 up-expression, ATP or BzATP-evoked [Ca2+]i rises as well as IL-6 release in PC12 cells exposed to high FFAs. Therefore, high concentrations of FFAs increased the expression of P2X7 in PC12 cells via activation of p38 mitogen-activated protein kinase (MAPK) signaling pathway, which contributed to P2X7-mediated IL-6 release from PC12 cells.
    Brain research bulletin 02/2013; · 2.18 Impact Factor
  • Han Liu, Jianuo Liu, Shangdong Liang, Huangui Xiong
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    ABSTRACT: Plasma gelsolin (pGSN), a secreted form of gelsolin, is constitutively expressed throughout the central nervous system (CNS). The neurons, astrocytes and oligodendrocytes are the major sources of pGSN in the CNS. It has been shown that levels of pGSN in the cerebrospinal fluid (CSF) are decreased in several neurological conditions including HIV-1-associated neurocognitive disorders (HAND). Although there is no direct evidence that a decreased level of pGSN in CSF is causally related to the pathogenesis of neurological disorders, neural cells, if lacking pGSN, are more vulnerable to cell death. To understand how GSN levels relate to neuronal injury in HAND, we studied the effects of pGSN on HIV-1 gp120-activated outward K+ currents in primary rat cortical neuronal cultures. Incubation of rat cortical neurons with gp120 enhanced the outward K+ currents induced by voltage steps and resulted in neuronal apoptosis. Treatment with pGSN suppressed the gp120-induced increase of delayed rectifier current (IK) and reduced vulnerability to gp120-induced neuronal apoptosis. Application of Guangxitoxin-1E (GxTx), a Kv2.1 specific channel inhibitor, inhibited gp120 enhancement of IK and associated neuronal apoptosis, similar effects to pGSN. Western blot and PCR analysis revealed gp120 exposure to up-regulate Kv2.1 channel expression, which was also inhibited by treatment with pGSN. Taken together, these results indicate pGSN protects neurons by suppressing gp120 enhancement of IK through Kv2.1 channels and reduction of pGSN in HIV-1-infected brain may contribute to HIV-1-associated neuropathy.
    Molecular and Cellular Neuroscience 01/2013; 57:73–82. · 3.84 Impact Factor
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    ABSTRACT: Chemokines and their receptors have the key role in inflammatory responses. The phenomenon of low grade inflammation is associated with the development of type 2 diabetes. Postprandial hyperglycemia increases the systemic inflammatory responses, which promotes the development of type 2 diabetic associating autonomic nervous injuries or cardiovascular disease. Neferine is a bisbenzylisoquinline alkaloid isolated from a Chinese medicinal herb. The objectives of this study will examine the CCL5 and CCR5 expression in the superior cervical ganglion (SCG) of type 2 diabetic rats. The effects of neferine on the expression of CCL5 and CCR5 mRNA and protein in the superior cervical ganglion (SCG) of type 2 diabetic rats will also be observed. The studies showed that in type 2 diabetic rats, body weight, blood pressure, heart rates, fasting blood glucose, insulin, total cholesterol and triglyceride were enhanced and high density lipoprotein was decreased, and CCL5 and CCR5 expression levels in the SCG of type 2 diabetic rats were up-regulated. In type 2 diabetic rats treated with neferine, body weight, blood pressure, fasting blood glucose, insulin, total cholesterol and triglyceride were decreased and high density lipoprotein was increased. The elevated expressions of CCL5 and CCR5 in SCG were decreased after type 2 diabetic rats treated with neferine. The motor nerve conduction velocity (MNCV) in diabetic rats treated with neferine group showed a significantly increment in comparison with that in type 2 diabetic group. Neferine can decrease the expression of CCL5 and CCR5 in the SCG and reduce the SCG neuronal signaling mediated by CCL5 and CCR5 in regulating diabetic cardiovascular autonomic complications.
    Brain research bulletin 10/2012; · 2.18 Impact Factor
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    ABSTRACT: BACKGROUND: Burn injury can induce an inflammatory response in the blood and wound of patients. Procedural activities in burn patients are particularly problematic in burn care due to their high intensity and frequency; hence, procedural pain evoked by burn dressing changes is a common severe issue. Previous studies demonstrated that purinergic signalling is one of the major pathways involved in the initiation, progression and down-regulation of the inflammatory response. Adenosine 5'-triphosphate (ATP) contributes to inflammation, and increased extracellular ATP levels amplify inflammation in vivo via the P2X(7) receptor. In the present study, the effect of puerarin, an active ingredient extracted from Chinese herbal medicine Ge Gen, on pain relief of burn patients during dressing change and the mechanism related to the regulation of the purinergic signalling pathway were investigated. METHODS: Burn patients were randomly divided into the normal saline group (NS-treated burn patients) and the puerarin-treated group (PUE-treated burn patients), and healthy volunteers were recruited as a control group. The visual Analogue Scale (VAS) scores, heart rate (HR) and respiratory rate (RR) of NS- and PUE-treated burn patients were observed. In addition, interleukin (IL)-1 and IL-4 levels in blood samples, as well as expression of P2X(7) receptor messenger RNA (mRNA) and protein in peripheral blood mononuclear cells (PBMCs) were determined. RESULTS: The IL-1 levels in the PUE-treated burn patients at post-dressing changes were significantly decreased in comparison with those in NS-treated burn patients; in contrast, the IL-4 levels in PUE-treated burn patients were increased. The expression levels of P2X(7) protein and mRNA in PBMCs of PUE-treated burn patients were significantly decreased in comparison with those in NS-treated burn patients. CONCLUSIONS: The inflammation and associated pain involved in dressing changes of burn patients were relieved by puerarin treatment. The effects were correlated with the decreased expression level of P2X(7) receptor mRNA and protein in PBMCs of burn patients.
    Burns: journal of the International Society for Burn Injuries 10/2012; · 1.95 Impact Factor
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    ABSTRACT: We investigated whether the expressions of CCL5 and CCR5 participate in dysfunctional changes in human umbilical vein endothelial cells (HUVECs) induced by chronic high glucose treatment and examined whether neferine exerts its therapeutic effects by blocking the development of dysfunctional vascular endothelium. HUVECs were cultured with control or high concentrations of glucose in the absence or presence of neferine for 5 days. Nitric acid reductase method was used to detect the concentration of nitric oxide (NO) released into culture media. The level of intracellular reactive oxygen species (ROS) was measured by fluorescent DCFH-DA probe. The expressions of 84 genes related to endothelial cell biology were assessed by Human Endothelial Cell Biology RT(2) Profiler PCR Array. The expressions of the chemokine CCL5 and its receptor CCR5 were further determined by real-time RT-PCR and western blotting. PCR array indicated that CCL5 was the most significantly upregulated when HUVECs were exposed to chronic high glucose; the intracellular ROS level and the expressions of CCL5 and CCR5 at both mRNA and protein levels were significantly increased, whereas NO production was decreased simultaneously. The increased level of ROS and elevated expressions of CCL5 and CCR5 at high glucose were significantly inhibited by neferine; meanwhile the decreased NO production upon chronic high glucose treatment was relieved. An antioxidant (vitamin E) exerted similar beneficial effects. These data indicate that neferine can reduce the upregulation of CCL5 and CCR5 of vascular endothelium exposure to chronic high glucose and prevent or inhibit subsequent occurrence of inflammation in blood vessels possibly through antioxidation.
    Inflammation 09/2012; · 2.46 Impact Factor
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    ABSTRACT: Neuropathic pain can arise from a lesion affecting the peripheral nervous system. Selective P2X3 and P2X2/3 receptors’ antagonists effectively reduce neuropathic pain. VEGF inhibitors are effective for pain relief. The present study investigated the effects of Vatalanib (VEGF receptor-2 (VEGFR-2) inhibitor) on the neuropathic pain to address the interaction of VEGFR-2 and P2X2/3 receptor in dorsal root ganglia of chronic constriction injury (CCI) rats. Neuropathic pain symptoms following CCI are similar to most peripheral lesions as assessed by the Neuropathic Pain Symptom Inventory. Sprague-Dawley rats were randomly divided into sham group, CCI group and CCI rats treated with Vatalanib group. Mechanical withdrawal threshold and thermal withdrawal latency were measured. Co-expression of VEGFR-2 and P2X2 or P2X3 in L4-6 dorsal root ganglia (DRG) was detected by double-label immunofluorescence. The modulation effect of VEGF on P2X2/3 receptor agonist-activated currents in freshly isolated DRG neurons of rats both of sham and CCI rats was recorded by whole-cell patch-clamp technique. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in CCI group were lower than those in sham group (p < 0.05). MWT and TWL in CCI rats treated with Vatalanib group were increased compared with those in CCI group (p < 0.05). VEGFR-2 and P2X2 or P2X3 receptors were co-expressed in the cytoplasm and surface membranes of DRG. The co-expression of VEGFR-2 and P2X2 or P2X3 receptor in CCI group exhibited more intense staining than those in sham group and CCI rats treated with Vatalanib group, respectively. VEGF enhanced the amplitude of ATP and α,β-meATP -activated currents of both sham and CCI rats. Increment effects of VEGF on ATP and α,β-meATP -activated currents in CCI rats were higher than those in sham rats. Both ATP (100 μM) and α,β-meATP (10 μM)- activated currents enhanced by VEGF (1 nM) were significantly blocked by Vatalanib (1 μM, an inhibitor of VEGF receptors). The stain values of VEGFR-2, P2X2 and P2X3 protein expression in L4/5 DRG of CCI treated with Vatalanib group were significantly decreased compared with those in CCI group (p < 0.01). Vatalanib can alleviate chronic neuropathic pain by decreasing the activation of VEGF on VEGFR-2 and the positive interaction between the up-regulated VEGFR-2 and P2X2/3 receptors in the neuropathic pain signaling.
    Neurochemistry International 05/2012; 60(6):565–572. · 2.66 Impact Factor
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    ABSTRACT: For transcriptome analysis, it is critical to precisely define all the transcripts across the whole genome. More and more digital gene expression (DGE) scannings have indicated the presence of huge amount of novel transcripts in addition to the known gene models. However, almost all these studies still depend crucially on existing annotation. Here, we present Gene2DGE, a Perl software package for gene model renewal with DGE data. We applied Gene2DGE to the mouse blastomere transcriptome, and defined 98,532 read-enriched regions (RERs) by read clustering supported by more than four reads for each base pair. Taking advantage of this ab initio method, we refined 2,104 exonic regions (4% of a total of 48,501 annotated transcribed regions) with remarkable extension into un-annotated regions (>50 bp). For 5% of uniquely mapped reads falling within intron regions, we identified 13,291 additional possible exons. As a result, we renewed 4,788 gene models, which account for 39% of a total of 12,277 transcribed genes. Furthermore, we identified 12,613 intergenic RERs, suggesting the possible presence of novel genes outside the existing gene models. In this study, therefore, we have developed a suitable tool for renewal of known gene models by ab initio prediction in transcriptome dissection. The Gene2DGE package is freely available at http://bighapmap.big.ac.cn/.
    Genomics Proteomics & Bioinformatics 02/2012; 10(1):51-4.
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    ABSTRACT: Neuropathic pain is caused by the peripheral or central nervous system structure damage or dysfunction. VEGF is involved in nociception and inflammation. VEGF may target VEGF receptor-2 (VEGFR-2) on the surface of neurons. P2X(2/3) receptors play a crucial role in facilitating pain transmission at the spinal sites. Chronic constriction injury (CCI) rats were used as neuropathic pain model. Sprague-Dawley male rats were randomly divided into sham group, anti-recombinant VEGF antibody group with phosphate-buffer saline (anti-rVEGF+PBS group), CCI rats treated with phosphate-buffer saline group (CCI+PBS group) and CCI rats treated with anti-recombinant VEGF antibody group (CCI+anti-rVEGF group). The expressions of VEGFR-2, P2X(2) and P2X(3) protein in spinal dorsal horn (SDH) were detected by immunohistochemistry, double-label immunofluorescence and western blotting. The protein levels of VEGFR-2, P2X(2) and P2X(3) in L4/5 SDH of CCI+PBS group were higher than those in sham group. VEGFR-2 and P2X(2) or P2X(3) receptors were co-expressed in the cytoplasm and surface membranes of SDH. Anti-rVEGF treatment in CCI rats reduced the expression of VEGFR-2 and P2X(2/3) receptors in L4/5 SDH compared with those in CCI+PBS group. Therefore, VEGF may activate VEGFR-2 to participate the process of neuropathic pain. Anti-rVEGF treatment in CCI rats reduced the expression of VEGFR-2 and inhibited the transmission of neuropathic pain in L4/5 SDH via decreasing the expression of P2X(2/3). There is a cross-potentiation between VEGFR-2 and P2X(2/3) receptors in neuropathic pain state.
    Brain research bulletin 12/2011; 87(2-3):227-33. · 2.18 Impact Factor
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    ABSTRACT: Tissue injury or inflammation of the nervous system may result in chronic neuropathic pain characterized by sensitivity to painful stimuli. P2X(3) receptors play a crucial role in facilitating pain transmission. Puerarin is an active compound of a traditional Chinese medicine Ge-gen, and Ge-gen soup has anti-inflammatory effects. The present research investigated the role of puerarin in the signalling of chronic neuropathic pain mediated by P2X(3) receptors of rat dorsal root ganglion neurons. Chronic constriction injury (CCI) rat model was adopted. Sprague-Dawley rats were randomly divided into blank control group (Ctrl), sham group (Sham), puerarin-treated control group (Ctrl+PUE), chronic constriction injury (CCI) group and puerarin-treated CCI group (CCI+PUE). Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by the von-Frey test and the Hargreaves' test respectively. The stain values of P2X(3) protein and mRNA in L4/L5 dorsal root ganglion (DRG) were detected by immunohistochemistry, western blot and in situ hybridization. At day 4-7 after the operation of CCI rats, MWT and TWL in group CCI and CCI+PUE were lower than those in group Ctrl, Sham and Ctrl+PUE, while there was no difference among group Ctrl, Sham and Ctrl+PUE. At day 7-10 after operation, MWT and TWL in group CCI+PUE was higher than those in group CCI, but there was no significant difference between group CCI+PUE and group Ctrl (p>0.05). At day 14 after operation, the stain values of P2X(3) proteins and mRNAs in L4/L5 DRG of group CCI were higher than those in group Ctrl, Sham, Ctrl+PUE and CCI+PUE, while the stain values of P2X(3) proteins and mRNAs in group CCI+PUE were significantly decreased compared with those in group CCI. Therefore, puerarin may alleviate neuropathic pain mediated by P2X(3) receptors in dorsal root ganglion neurons.
    Brain research bulletin 10/2011; 87(1):37-43. · 2.18 Impact Factor
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    ABSTRACT: Pain is a major problem after burns. Procedural pain evoked by burn dressing changes is common in patients, and its management is a critical part of treatment in acute burn injuries. Burn pain is very likely the most difficult form of acute pain to treat. ATP contributes to inflammation, and ATP is implicated in peripheral pain signaling via actions upon P2X(3) receptors. Puerarin is extracted from a traditional Chinese medicine and may act on P2X(3) receptor mechanisms. The Visual Analogue Scale (VAS) has been shown to be a sensitive indicator of pain intensity and treatment effects. Peripheral blood mononuclear cells (PBMCs) are involved in nociception or pain after burn injury. Burn patients were randomly divided into normal saline (NS) group (salt solution is saline) and puerarin-treated group and pain (Visual Analogue Scale scores) and inflammation (PBMCs) measured. Burn pain produces a stress response, so blood glucose, insulin, and cortisol levels in burn patients were determined. Furthermore, the expression of P2X(3) protein and mRNA in PBMCs was detected. The VAS scores in the puerarin-treated group were lower than those in NS group. The blood glucose, insulin, and cortisol levels in the puerarin-treated group at post-dressing changes were significantly decreased in comparison with those in NS group. The expression levels of P2X(3) protein and mRNA in PBMCs of burn patients in NS group were significantly increased in comparison with those in the puerarin-treated group. Puerarin can antagonize inflammatory factors (such as ATP) and decrease the upregulated expressions of P2X(3) protein and mRNA in PBMCs after burns to decrease VAS. Thus, puerarin had an analgesic effect on procedural pain in dressing changes of burn patients related to P2X(3) receptors.
    Purinergic Signalling 07/2011; 7(4):489-97. · 2.64 Impact Factor
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    ABSTRACT: Microglia are critical cells in mediating the pathophysiology of neurodegenerative disorders such as HIV-associated neurocognitive disorders. We hypothesize that HIV-1 glycoprotein 120 (gp120) activates microglia by enhancing outward K(+) currents, resulting in microglia secretion of neurotoxins, consequent neuronal dysfunction, and death. To test this hypothesis, we studied the effects of gp120 on outward K(+) current in cultured rat microglia. Application of gp120 enhanced outward K(+) current in a dose-dependent manner, which was blocked by voltage-gated K(+) (K(v) ) channel blockers. Western blot analysis revealed that gp120 produced an elevated expression of K(v) channel proteins. Examination of activation and inactivation of outward K(+) currents showed that gp120 shifted membrane potentials for activation and steady-state inactivation. The gp120-associated enhancement of outward K(+) current was blocked by either a CXCR4 receptor antagonist T140 or a specific protein kinase A (PKA) inhibitor H89, suggesting the involvement of chemokine receptor CXCR4 and PKA in gp120-mediated enhancement of outward K(+) current. Biological significance of gp120-induced enhancement of microglia outward K(+) current was demonstrated by experimental results showing the neurotoxic activity of gp120-stimulated microglia, evaluated by TUNEL staining and MTT assay, significantly attenuated by K(v) channel blockers. Taken together, these results suggest that gp120 induces microglia neurotoxic activity by enhancing microglia outward K(+) current and that microglia K(v) channels may function as a potential target for the development of therapeutic strategies.
    Glia 03/2011; 59(6):997-1007. · 5.07 Impact Factor
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    ABSTRACT: Neuropathic pain is the most difficult type of pain to cure. The P2X(2/3) receptors play a crucial role in facilitating the transmission of pain at neuropathic pain states. Emodin is a natural anthraquinone in rhubarb. The present research investigated the effects of emodin on the pain transmission in neuropathic pain states that was mediated by P2X(2/3) receptor in primary sensory neurons. Chronic constriction injury (CCI) model was used as neuropathic pain model. Emodin was dissolved in 0.5% sodium carboxymethyl cellulose (CMC) as vehicle. Sprague-Dawley male rats had been randomly divided into Sham+vehicle group, CCI+emodin group, and CCI+vehicle group. Mechanical withdrawal threshold and thermal withdrawal latency were measured. P2X(2/3) expression in L4/L5 dorsal root ganglion (DRG) was detected by immunohistochemistry, in situ hybridization (ISH) and RT-PCR. The mechanical withdrawal threshold and thermal withdrawal latency in CCI+vehicle group were lower than those in Sham+vehicle group and CCI+emodin group (p<0.05), while P2X(2) and P2X(3) receptor expression of L4/L5 DRG in CCI+vehicle group was higher than those in the other two groups (p<0.05). The co-local staining of P2X(2) and P2X(3) in the DRG of CCI group appeared to be more intense than that in the DRG of the other two groups with double-label fluorescence immunohistochemistry. The results showed that the application of emodin alleviated the hyperalgesia of CCI rats and significantly decreased the P2X(2/3) expression of L4/L5 DRG in CCI+emodin group compared with that in CCI+vehicle group (p<0.05). The data of ISH and RT-PCR in P2X(2) and P2X(3) mRNA expression suggest that the pharmacologic mechanism of emodin is involved in the nucleic acid level. The results showed that emodin can inhibit the transmission of neuropathic pain mediated by P2X(2/3) receptor of primary sensory neurons to alleviate chronic neuropathic pain.
    Brain research bulletin 02/2011; 84(6):406-13. · 2.18 Impact Factor

Publication Stats

186 Citations
81.21 Total Impact Points

Institutions

  • 2012–2013
    • Nanchang University
      Nan-ch’ang-shih, Jiangxi Sheng, China
  • 2011
    • University of Nebraska at Omaha
      • Department of Pharmacology and Experimental Neuroscience
      Omaha, NE, United States
  • 2010
    • Tongji Medical University
      Wu-han-shih, Hubei, China