Yong-Mei Zhang

Xuzhou Medical College, Suchow, Jiangsu Sheng, China

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Publications (30)39.2 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Microglia play an important role in neuronal protection and damage. However, the molecular and cellular relationship between microglia and neurons is unclear. We carried out a prospective study to detect that activation of BV2 microglia induced PC12 cell apoptosis in vitro through the TLR4/adapter protein myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. BV2 microglia were treated with different concentrations of LPS for 24 h. Western blot was utilized to detect the expression of TLR4 and the downstream signaling pathway. The level of inflammatory mediator was quantified using a specific ELISA kit. The supernatant of 10 μg/ml LPS-treated BV2 cells was used as conditioned medium (CM). PC12 cells were co-culture with CM for 24 h. Cell viability was determined by MTT assay and cell apoptosis was tested by flow cytometry. BV2 microglia were treated with 10, 20, or 30 μg/ml LPS for 24 h. The expression of TLR4, MyD88, and NF-κB significantly increased. When PC12 cells were co-cultured with CM for 24 h, cell viability decreased. CM up-regulated the Bax level and down-regulated the Bcl-2 protein level in PC12 cells. PC12 cells pretreated with interleukin-1 receptor antagonist (IL-1RA) for 30 min, significantly alleviated CM-induced PC12 cell apoptosis. These results suggest that BV2 microglia activated by LPS triggered TLR4/MyD88/NF-κB signaling pathway that induced the release of IL-1β and could participate in the PC12 cells injury.
    Cell Stress and Chaperones 11/2014; · 2.48 Impact Factor
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    ABSTRACT: The aim of the paper is to study the effect of spontaneous firing of injured dorsal root ganglion (DRG) neuron in chronic compression of DRG (CCD) model on excitability of wide dynamic range (WDR) neuron in rat spinal dorsal horn. In vivo intracellular recording was done in DRG neurons and in vivo extracellular recording was done in spinal WDR neurons. After CCD, incidence of spontaneous discharge and firing frequency enhanced to 59.46% and (4.30 ± 0.69) Hz respectively from 22.81% and (0.60 ± 0.08) Hz in normal control group (P < 0.05). Local administration of 50 nmol/L tetrodotoxin (TTX) on DRG neuron in CCD rats decreased the spontaneous activities of WDR neurons from (191.97 ± 45.20)/min to (92.50 ± 30.32)/min (P < 0.05). On the other side, local administration of 100 mmol/L KCl on DRG neuron evoked spontaneous firing in a reversible way (n = 5) in silent WDR neurons of normal rats. There was 36.36% (12/33) WDR neuron showing after-discharge in response to innocuous mechanical stimuli on cutaneous receptive field in CCD rats, while after-discharge was not seen in control rats. Local administration of TTX on DRG with a concentration of 50 nmol/L attenuated innocuous electric stimuli-evoked after-discharge of WDR neurons in CCD rats in a reversible manner, and the frequency was decreased from (263 ± 56.5) Hz to (117 ± 30) Hz (P < 0.05). The study suggests that the excitability of WDR neurons is influenced by spontaneous firings of DRG neurons after CCD.
    Sheng li xue bao: [Acta physiologica Sinica] 10/2013; 65(5):533-539.
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    ABSTRACT: To investigate the association of traumatic severity with changes in lymphocyte subsets in the early stage after trauma. Sixty-three male patients admitted within 4 hours after trauma were enrolled. According to injury severity score (ISS), the patients were divided into two groups: mild trauma group (ISS<16, n=35) and severe trauma group (ISS≥16, n=28). At admission, the patients peripheral blood were extracted to detect T lymphocytes subsets, blood routine test, blood biochemical and arterial blood gas analysis which were used to calculate the acute physiology and chronic health evaluation II (APACHEII) scores. The correlation of lymphocyte subsets and ISS score, and the correlation of lymphocyte subsets and APACHEII score were both analyzed statistically. Another 20 cases of healthy male adults were enrolled as the control group. Compared with the healthy control group, CD3(+) T cell contents in blood were decreased obviously in mild trauma group and severe trauma group (0.648±0.112, 0.647±0.110 vs. 0.708±0.082, both P<0.05); CD4(+) T cells contents in severe group were decreased significantly (0.317±0.086 vs. 0.389±0.064, P<0.05), and natural killer (NK) cells were significantly increased (0.217±0.107 vs. 0.158±0.068, P<0.05). B cells content in severe group was decreased significantly than that of mild group (0.114±0.060 vs. 0.155±0.075, P<0.05). There were no significant difference in CD8(+) and CD4/CD8 ratio among the healthy control group, mild trauma group and severe trauma group (CD8(+): 0.260±0.074, 0.260±0.091, 0.271±0.105; CD4/CD8 ratio: 1.69±0.75, 1.56±0.83, 1.34±0.65, all P>0.05). Except that there were negative correlation between CD3(+) T cells and the ISS scores (r=-0.42, P=0.03), the other lymphocyte subsets showed no correlation with the ISS scores and the APACHEII scores (mild trauma group with ISS scores: CD3(+) r=-0.10, CD4(+) r=-0.31, CD8(+) r=0.18, B cells r=0.20, NK cells r=-0.04; mild trauma group with APACHEII scores: CD3(+) r=0.04, CD4(+) r=-0.07, CD8(+) r=0.06, B cells r=-0.10, NK cells r=0.05, severe trauma group with ISS scores: CD4(+) r=-0.12, CD8(+) r=-0.17, B cells r=0.02, NK cells r=0.31,all P>0.05;severe trauma group with APACHEII scores:CD3(+) r=-0.24, CD4(+) r=0.11, CD8(+) r=-0.26, B cells r=0.15, NK cells r=0.08, all P>0.05). CD3(+) and CD4(+) T cells decreased and NK cells increased significantly in blood in the early stage after severe trauma. CD3(+) T cells are independent indexes which reflect body injury. Therefore, it is necessary to monitor the changes of immune cells dynamically after severe trauma.
    Zhonghua wei zhong bing ji jiu yi xue. 08/2013; 25(8):489-92.
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    ABSTRACT: BACKGROUND AND AIMS: Toll-like receptor 4 (TLR4) contributes to ethanol-induced gastric mucosal injury. This study aimed to determine its precise role in this pathogenic state and the related signaling pathway. METHODS: Ethanol-induced gastric mucosal injury models were generated in TLR4(-/-) mice (C3H/HeJ: point mutation; C57BL/10ScNJ: gene deletion), their respective TLR4(+/+) wild-type counterparts, and heterozygous TLR4(+/-) mice. Lipopolysaccharide (LPS) or pyrrolidine dithiocarbamate (PDTC) was injected intraperitoneally 1 h or 30 min before ethanol administration. At 1 h post-ethanol treatment, gastric or serum specimens were evaluated. RESULTS: Ethanol intra-gastric administration induced significant gastric mucosal injury in all mice, but the damaged area was larger in TLR4(-/-) mice. LPS preconditioning and up-regulated TLR4 expression led to significantly larger areas of gastric mucosal damage. Upon ethanol administration, TLR4(+/+), and not TLR4(-/-), mice showed significant increases in TLR4, myeloid differentiation factor 88 (MyD88), cytoplasmic high mobility group box 1 (HMGB1), and nuclear factor-kappa B p65 (NF-κB p65). PDTC pretreatment significantly attenuated the ethanol-induced gastric mucosal damaged areas, inhibited nuclear NF-κB p65 expression, and suppressed HMGB1 translocation out of the nucleus. In addition, PDTC pretreatment reduced ethanol-stimulated expression of the inflammatory modulators, interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α), in serum. CONCLUSIONS: Both deficient and excessive expression of TLR4 promotes ethanol-induced gastric mucosal injury. The underlying mechanism involves the MyD88/NF-κB signaling pathway and the HMGB1, TLR4 activator ligand. The increased expression of HMGB1 may lead to increased secretion and binding to TLR4, further stimulating the TLR4/MyD88/NF-κB signaling pathway and aggravating the ethanol-induced gastric mucosal injury.
    Digestive Diseases and Sciences 06/2013; · 2.26 Impact Factor
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    ABSTRACT: This study aimed to investigate the role of the Toll-like receptor 4 (TLR4) pathway in normal human gastric epithelial (GES-1) cells under hypoxia/reoxygenation (H/R) in vitro, and the effect of propofol on injured GES-1 cells as well as its possible mechanism. Before H/R induction, GES-1 cells were preconditioned with fat emulsion, propofol, or epigallocatechin gallate. Then cell viability, cell apoptosis, and related molecules in the cells were analyzed under experimental conditions. We found that propofol 50 μmol/L markedly inhibited the H/R injury under hypoxia 1.5 h/reoxygenation 2 hours by promoting GES-1 cell viability and decreasing cell apoptosis. The TLR4 signal may be involved in the protective effect of propofol against H/R injury. The malondialdehyde contents and superoxide dismutase activities were recovered under propofol preconditioning. In summary, propofol preconditioning may exert a protective effect on H/R injury in GES-1 cells and the mechanism may be via inhibition of the activated TLR4 signal under H/R conditions.
    The Kaohsiung journal of medical sciences 06/2013; 29(6):289-298. · 0.50 Impact Factor
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    ABSTRACT: Propofol exhibits neuroprotective effects against hypoxic-ischemic brain injury, but the underlying mechanisms are still not clear. Toll-like receptor 4 (TLR4) plays a considerable role in the induction of innate immune and inflammatory responses. The purposes of this study are to investigate the effect of propofol on the oxygen and glucose deprivation (OGD)/reoxygenation (OGD/R) BV2 microglia and to explore the role of TLR4/myeloid differentiation protein 88 (MyD88)/nuclear factor-kappa B (NF-κB) pathway in the neuroprotective effects of propofol. BV2 microglia were placed into an airtight chamber and in glucose-free medium for OGD/reoxygenation. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. TLR4 and its downstream signaling molecules, MyD88 and NF-κB expressions were detected by Western blotting. Level of tumor necrosis factor alpha (TNF-α) in culture medium was determined with enzyme-linked immunosorbent assay. BV2 microglia apoptosis was determined by flow cytometry. We found that pretreatment with propofol significantly alleviated the hypoxic injury in BV2 microglia. Propofol inhibited upregulation of TLR4, MyD88, and NF-κB expressions in BV2 microglia exposed to OGD/reoxygenation. Propofol pretreatment also significantly reduced the production of TNF-α and apoptosis in OGD/reoxygenation BV2 microglia. The results indicated that TLR4 and its downstream MyD88-dependent signaling pathway contributed to neuroprotection of propofol to microglia exposed to OGD/reoxygenation.
    Journal of physiology and biochemistry 03/2013; · 1.65 Impact Factor
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    ABSTRACT: Pituitary adenylate cyclase-activating polypeptide (PACAP) is effective in reducing axonal damage associated with traumatic brain injury (TBI), and has immunomodulatory properties. Toll-like receptor 4 (TLR4) is an important mediator of the innate immune response. It significantly contributes to neuroinflammation induced by brain injury. However, it remains unknown whether exogenous PACAP can modulate TBI through the TLR4/adapter protein myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. In this study, we investigated the potential neuroprotective mechanisms of PACAP pretreatment in a weight-drop model of TBI. PACAP38 was microinjected intracerebroventricularly before TBI. Brain samples were extracted from the pericontusional area in the cortex and hippocampus. We found that TBI induced significant upregulation of TLR4, with peak expression occurring 24 h post-trauma, and that pretreatment with PACAP significantly improved motor and cognitive dysfunction, attenuated neuronal apoptosis, and decreased brain edema. Pretreatment with PACAP inhibited upregulation of TLR4 and its downstream signaling molecules MyD88, p-IκB, and NF-κB, and suppressed increases in the levels of the downstream inflammatory agents interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), in the brain tissue around the injured cortex and in the hippocampus. Administration of PACAP both in vitro and in vivo attenuated the ability of the TLR4 agonist lipopolysaccharide (LPS) to increase TLR4 protein levels. Therefore, PACAP exerts a neuroprotective effect in this rat model of TBI, by inhibiting a secondary inflammatory response mediated by the TLR4/MyD88/NF-κB signaling pathway in microglia and neurons, thereby reducing neuronal death and improving the outcome following TBI.
    Journal of neurotrauma 05/2012; 29(10):1941-59. · 4.25 Impact Factor
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    ABSTRACT: The neuroprotective effects of pituitary adenylate cyclise-activating polypeptide (PACAP) have been well documented in vivo and in vitro. However, the mechanisms by which PACAP protected microglia from ischemic/hypoxic injury via inhibition of microglia activation remain unclear. Toll-like receptor 4 (TLR4) plays a considerable role in the induction of innate immune and inflammatory responses. The purpose of this study is to investigate the effect of PACAP on the oxygen and glucose deprivation (OGD)/reoxygenation BV2 microglia and to explore the role of TLR4/myeloid differentiation protein 88 (MyD88)/nuclear factor-kappa B (NF-kappaB) pathway in the neuroprotective effects of PACAP. We conducted OGD/reoxygenation by placing BV2 microglia into an airtight chamber and in glucose-free medium. BV2 microglia cell viability was determined by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay. Western blot was utilized to detect TLR4, MyD88 expression, inhibitory protein of NF-kappaB (IkappaB) phosphorylation/degradation, NF-kappaB activation. Level of tumor necrosis factor-alpha (TNF-alpha) in culture medium was measured with enzyme-linked immunosorbent assay (ELISA). Apoptosis was determined by flow cytometry. We found that pretreatment with PACAP to BV2 cells immediately before OGD/reoxygenation significantly alleviated microglia hypoxic injury. PACAP inhibited upregulation of TLR4, MyD88 and NF-kappaB in BV2 microglial cells exposed to OGD/reoxygenation. PACAP administration also significantly reduced the production of proinflammatory cytokines and apoptosis in BV2 microglia exposed to OGD/reoxygenation. Pretreatment with PACAP inhibited activation of the TLR4/MyD88/NF-kappaB signaling pathway and decreased inflammatory cytokine levels, as well as apoptosis in microglia, thereby attenuating microglia hypoxic injury. Our results suggested that TLR4-mediated MyD88-dependent signaling pathway contributed to neuroprotection of PACAP to microglia against OGD/reoxygenation.
    Neurological Research 05/2012; 34(4):379-89. · 1.18 Impact Factor
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    ABSTRACT: AIMS: Propofol has demonstrated protective effects against digestive injury. Toll-like receptor-4 (TLR4) is involved in gastric mucosal injury. However, it has not yet been clarified whether propofol protects gastric mucosa from ethanol-induced injury and whether the mechanism involved is related to TLR4 activation. Therefore, this prospective study was carried out to address the issue. METHODS: Gastric mucosal injury was induced in mice by intragastric administration of ethanol. Propofol was given intraperitoneally 30min before ethanol intragastric administration and, 1h later, gastric specimens were studied using hematoxylin-eosin staining, quantitative real-time RT-PCR, immunohistochemical staining and Western blot assays; serum specimens were studied using ELISA kits. RESULTS: Propofol at 25mg/kg significantly attenuated ethanol-induced gastric mucosal injury. In addition, propofol pretreatment significantly inhibited the upregulated expression of high-mobility group box-1 (HMGB1) protein, TLR4 and its downstream signaling molecules-myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB)-in gastric mucosa, while suppressing the increased release of tumor neurosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum. Furthermore, upregulation of the Bax/Bcl-2 ratio in gastric mucosa was clearly depressed by propofol. CONCLUSION: Propofol can inhibit HMGB1 expression and TLR4/MyD88/NF-κB-mediated inflammatory responses, and hamper apoptosis, which may contribute to its protective action against ethanol-induced gastric mucosal injury.
    Gastroentérologie Clinique et Biologique 04/2012; · 0.80 Impact Factor
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    ABSTRACT: The effect of pituitary adenylate cyclase activating polypeptide (PACAP) during traumatic brain injury (TBI) and whether it can modulate secondary injury has not been reported previously. The present study evaluated the potential protective effects of ventricular infusion of PACAP in a rat model of TBI.
    World journal of emergency medicine. 01/2012; 3(4):294-8.
  • Shan-shan Mao, Yong-mei Zhang
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    ABSTRACT: In the central nervous system, pituitary adenylate cyclase-activating polypeptide (PACAP) exerts different actions as neurotransmitter, neuromodulator, neurotrophic and neuroprotective factors via multiple signaling pathways. PACAP plays an important protective role in the nervous system diseases, such as focal cerebral ischemia, traumatic brain injury (TBI), schizophrenia, anxiety disorders Parkinson's disease and Alzheimer's disease. Now, we reviewed the research advances about the protective role of PACAP in the nervous system diseases.
    Sheng li ke xue jin zhan [Progress in physiology] 08/2011; 42(4):276-80.
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    ABSTRACT: Previously we demonstrated the neuroprotective effect of montelukast, a cysteinyl leukotriene receptor-1 (CysLT(1) ) antagonist, on acute brain injury after focal cerebral ischaemia in mice. In this study, we have determined its effect on chronic brain injury after focal cerebral ischaemia in mice and rats. After transient focal cerebral ischaemia was induced by middle cerebral artery occlusion, montelukast was intraperitoneally injected in mice or orally administered to rats for five days. Behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss were determined to evaluate brain lesions. Montelukast (0.1 mg/kg) attenuated behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss in mice, which was similar to pranlukast, another CysLT(1) receptor antagonist. Oral montelukast (0.5 mg/kg) was effective in rats and was more effective than edaravone, a free radical scavenger. Montelukast protected mice and rats against chronic brain injury after focal cerebral ischaemia, supporting the therapeutic potential of CysLT(1) receptor antagonists.
    The Journal of pharmacy and pharmacology. 04/2011; 63(4):550-7.
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    ABSTRACT: The purpose of this study was to investigate the effects and mechanisms of 17beta-estradiol pharmacological postconditioning on gastric epithelial cells hypoxia/reoxygenation injury by using an in vitro model of human gastric epithelial cells. The model of hypoxia/reoxygenation was established with human gastric epithelial cell line. The gastric epithelial cell viability was detected by 3-(4, 5-dimethylthazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assays. Gastric epithelial cellular apoptosis was determined by Hoechst 33258 fluorochrome staining and flow cytometric analysis. Contents of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were measured by Colorimetry analysis. The protein expression of Bcl-2 and Bax in different groups was determined by Western blot analyses and immunocytochemistry assay. 17beta-estradiol (10(-8), 10(-7) and 10(-6)mol/l) inhibited hypoxia/reoxygenation injury and 17beta-estradiol (10(-6)mol/l) obviously attenuated hypoxia/reoxygenation injury 3h hypoxia followed by 4h reoxygenation. 17beta-estradiol promoted gastric epithelial cell viability and inhibited the gastric epithelial cell apoptosis, and meanwhile, decreased the MDA content and increased SOD activity. The level of Bcl-2 protein was restored to the normal level by 17beta-estradiol pharmacological postconditioning. In contrast, the Bax protein level was markedly reduced by 17beta-estradiol pharmacological postconditioning. These effects of 17beta-estradiol were inhibited by pretreatment with fulvestrant. These data suggested that 17beta-estradiol seems involved in regulation of gastric hypoxia/reoxygenation injury and gastroprotection, and its protective effects were strongly related to estrogen receptor.
    European journal of pharmacology 10/2010; 645(1-3):151-7. · 2.59 Impact Factor
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    ABSTRACT: No published study has addressed the effect of genistein postconditioning on gastric ischemia-reperfusion (GI-R) injury in rats. To examine whether capsaicin receptor-mediated genistein postconditioning protects against gastric ischemia-reperfusion injury via the PI3K/Akt signal pathway. Chloraldurat-anesthetized rats underwent occlusion of the celiac artery for 30 min, followed by 60 min of reperfusion. Based on this animal model of gastric ischemia-reperfusion injury, genistein at doses of 100, 500 or 1,000 μg/kg was administered via peripheral vein 5 min before reperfusion. The dose of 500 μg/kg was optimal for postconditioning, at which the severity of I-R-induced gastric injury significantly decreased. Immunohistochemistry also showed that gastric mucosal cell apoptosis decreased. Capsazepine (CPZ), a specific antagonist for the capsaicin receptor, was administered (1,000 μg/kg, i.v.) just before ischemia. Capsaicin (50 mg/kg, s.c.) once a day for 4 days reversed the protective effects of genistein. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed increased calcitonin gene-related peptide (CGRP) expression in genistein group but not in capsazepine or capsaicin group. CGRP inhibitor CGRP8-37 also prevented the effects of genistein in decreasing gastric mucosal injury index. In addition, PI3K inhibitor LY294002 (1.5 mg/kg) reversed the protective effect of genistein. Compared with genistein group, Western blots also demonstrated decreased Akt phosphorylation in LY294002 group. Our data suggest that capsaicin receptors mediated the protective effects of genistein postconditioning. CGRP secreted by activated capsaicin-sensitive neurons played an important role in the protective effects of genistein. PI3K/Akt pathway was also involved in the protective effects of genistein.
    Digestive Diseases and Sciences 03/2010; 55(11):3070-7. · 2.26 Impact Factor
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    ABSTRACT: To prepare and identify a polyclonal antibody against cysteinyl leukotriene receptor (CysLT(2)receptor). Rabbits were immunized with KLH-coupled CysLT(2) receptor peptide to prepare the polyclonal antibody (pAb). The titer of the pAb in rabbit plasma was detected by indirect ELISA, and the specificity of the pAb was tested by antigen blockade. The tissue distribution of CysLT(2) receptor was detected by Western blot and immunohistochemistry with the prepared pAb. The pAb showed a titer higher than 1/1047296, and was specific to CysLT(2) receptor, without cross-reaction with the antigens of CysLT(1) receptor and GPR17. A higher expression of CysLT(2) receptor in kidney, brain and lung of rats and mice was detected by Western blot analysis using the prepared pAb. The molecular weight of CysLT(2) receptor protein was about 40 kD. Immunohistochemical examination showed that CysLT(2) receptor was expressed mainly in the neuron, and partly in astrocytes in rat brain. The prepared CysLT(2) receptor pAb has high sensitivity and specificity, and can be used in Western blot and immunohistochemistry.
    Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 11/2009; 38(6):591-7.
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    ABSTRACT: In the present study, rat model of gastric ischemia-reperfusion (GI-R) injury was established by clamping the celiac artery for 30 min followed by 1 h of reperfusion. Subsequently, the regulatory effect of electrical stimulation of cerebellar fastigial nucleus (FN) on GI-R injury and its neural mechanisms were investigated in Sprague-Dawley rats. The results are as follows. Electrical stimulation of the cerebellar FN not only obviously attenuated the GI-R injury in an intensity-dependent manner, but also decreased the apoptosis rate of gastric mucosal cells. Chemical lesion of FN eliminated the protective effect of electrical stimulation of FN on GI-R injury. Electrical stimulation of cerebellar FN decreased both the frequency and amplitude of the discharges of greater splanchnic nerve, but it could not change the discharge of greater splanchnic nerve following the lesion of the lateral hypothalamic area (LHA). After bilateral section of the greater splanchnic nerves, electrical stimulation of the FN also attenuated the GI-R injury. Chemical lesion of the LHA reversed the protective effect of electrical stimulation of FN on GI-R injury. Electrical stimulation of FN increased the activity of superoxide dismutase (SOD), but decreased the content of malondialdehyde (MDA) in gastric mucosa under GI-R. These results indicate that the cerebellar FN may regulate GI-R injury. Therefore, the cerebellar FN is an important brain site protecting the stomach against GI-R. The LHA and greater splanchnic nerves participate in the regulatory effects of cerebellar FN stimulation on GI-R injury. In addition, antioxidation may also be involved in the protection mechanism of cerebellar FN stimulation.
    Sheng li xue bao: [Acta physiologica Sinica] 10/2009; 61(5):451-7.
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    ABSTRACT: To prepare and identify a polyclonal antibody (pAb) against GPR17, a novel cysteinyl leukotriene receptor. Rabbits were immunized with KLH-coupled GPR17 peptide to prepare the pAb. The titer of the pAb in rabbit plasma was detected by indirect ELISA, and the specificity of the pAb was tested by antigen blockade. GPR17 tissue distribution was detected by Western blot with the pAb. The pAb showed a titer as high as 1:16 364,and was not cross-reacted with the antigens of CysLT(1) and CysLT(2) receptors. A higher expression of GPR17 in the rat brain and heart was detected using the newly prepared pAb. The molecular weigh of GPR17 protein was about 43 kD. The prepared GPR17 pAb has high sensitivity and specificity,and can be used in Western blot for detecting GPR17.
    Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 08/2009; 38(4):357-61.
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    Yu Li, Jian-fu Zhang, Yong-mei Zhang, Xiao-bo Ma
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    ABSTRACT: The aim of this study was to investigate the protective effect of genistein postconditioning on hypoxia/reoxygenation-induced injury in human gastric epithelial cells and to begin a tentative discussion on the mechanism behind this protection. A model of hypoxia/reoxygenation-induced injury was established in the human gastric epithelial cell line (GES-1). All cells in our present study were randomly divided into five groups: a normal control group (N), a hypoxia/reoxygenation group (H/R), a genistein postconditioning group (GP), a capsazepine+genistein postconditioning group (C+GP) and a DMSO vehicle postconditioning group (DM). The methods used included MTT assays to test cell viability, flow cytometric analyses to quantify the percentage of cell apoptosis, Western blot analyses to measure the protein expression of calcitonin gene-related peptide (CGRP), Bcl-2, and Bax, and immunocytochemistry assays to detect the expression of CGRP in each group. The MTT assays indicated that the cell viabilities of the groups were 100.0%+/-0%, 51.4%+/-4.1%, 66.7%+/-2.0%, 56.1%+/-2.8%, and 50.7%+/-2.4%, respectively. Compared with the H/R group, the viability of the GP group was significantly increased (P<0.01). Flow cytometric analysis showed that the cell apoptosis percentage of each group was 2.28%+/-0.44%, 12.17%+/-2.15%, 5.40%+/-1.22%, 10.43%+/-1.37%, and 11.02%+/-2.19%, respectively. Western blot analysis demonstrated that CGRP, Bcl-2, and Bax were expressed in normal human gastric epithelial cells. Compared with the H/R group, the GP group exhibited increased expression of CGRP and Bcl-2 and decreased expression of Bax. Immunocytochemistry assays indicated that the number of CGRP-positive cells in the GP group was significantly increased. Genistein postconditioning has a protective effect on hypoxia/reoxygenation-induced injury in human gastric epithelial cells. The mechanism by which genistein exerts this protection may be via activation of cellular vanilloid receptor subtype 1, resulting in the generation of an endogenous protection substance, CGRP.
    Acta Pharmacologica Sinica 04/2009; 30(5):576-81. · 2.35 Impact Factor
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    ABSTRACT: Our previous study demonstrated that electrical stimulation of the hypothalamic paraventricular nucleus (PVN) protects against gastric ischemia-reperfusion (GI-R) injury, but it is still unknown whether angiotensin II (Ang II) in the PVN plays a role in the development of GI-R. The purpose of this study was to investigate the effect of Ang II in the PVN on GI-R injury. GI-R injury was induced in rats by clamping the celiac artery for 30 min, and then reperfusing for 30 min, 1 h, 3 h, 6 h or 24 h, respectively. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The extent of gastric mucosal damage was determined by gross and histological methods. We found that microinjection of pharmacological doses of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury, and that Ang II (30 ng) markedly attenuated GI-R injury at 1 h and 3 h after reperfusion. The effect of Ang II was prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg) into the lateral cerebral ventricle. Furthermore, the protective effect of Ang II on GI-R injury was abolished by propranolol (1 mg/kg, i.v.) or disconnection of the nerves innervating the adrenal glands, was augmented by sympathectomy or phentolamine (1 mg/kg, i.v.), and was not affected by subdiaphragmatic vagotomy or atropine (1 mg/kg, i.v.). These results indicate that the PVN is a responsive site for central Ang II-induced protection against GI-R injury. The central effects of Ang II are mediated by AT1 receptors in the PVN, and the peripheral effects by a sympathetic-adrenal gland/beta-adrenoceptor pathway.
    Brain Research 06/2008; 1212:25-34. · 2.88 Impact Factor
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    ABSTRACT: The purpose of this study was to elucidate the role of nuclear factor kappaB (NF-kappaB) in the development of gastric ischemia-reperfusion (GI-R) injury and in mediating the effects of angiotensin II (Ang II) in the paraventricular nucleus (PVN) on GI-R injury. GI-R injury was induced in rats by clamping the celiac artery for 30 min and then reperfusing for 1 h. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The expressions and levels of NF-kappaB (p65), IkappaB-alpha, and phosphorylated IkappaB-alpha in rat gastric mucosa were examined by Western blotting and immunohistochemistry. A laser Doppler flowmeter was used to assess gastric blood flow (GBF). Malondialdehyde (MDA) was determined using the thiobarbituric acid (TBA) method, and superoxide dismutase (SOD) activity was determined by the xanthine/xanthine oxidase method. Microinjection of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury. The levels and expressions of NF-kappaB (p65) and phosphospecific IkappaB-alpha protein increased 1 h after GI-R and were markedly reduced by microinjection of Ang II into the PVN. In contrast, the level and expression of IkappaB-alpha protein decreased 1 h after ischemia-reperfusion and recovered to the normal level by microinjection of Ang II into the PVN. The effects of Ang II were prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg) microinjected into the lateral cerebral ventricle. Inhibition of NF-kappaB activity by pyrrolidine dithiocarbamate (PDTC, 200 mg/kg) produced similar effects in rats subjected to ischemia-reperfusion with or without microinjection of Ang II into the PVN. Administration of PDTC attenuated gastric mucosal injury and suppressed the activation of NF-kappaB (p65). Ang II microinjection into the PVN increased GBF and decreased the MDA content but did not alter SOD activity in the gastric mucosa following ischemia-reperfusion. NF-kappaB plays a role in PVN Ang II-mediated protection against GI-R injury. These central effects of Ang II are mediated by AT1 receptors.
    Journal of Gastroenterology 02/2008; 43(9):687-98. · 3.79 Impact Factor

Publication Stats

93 Citations
39.20 Total Impact Points

Institutions

  • 2002–2013
    • Xuzhou Medical College
      • Department of Physiology
      Suchow, Jiangsu Sheng, China
  • 2012
    • 309th Hospital of the PLA
      Peping, Beijing, China
  • 2007–2009
    • Zhejiang University
      • • School of Medicine
      • • Department of Pharmacology
      Hangzhou, Zhejiang Sheng, China