Ying Luo

Fourth Military Medical University, Xi’an, Liaoning, China

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Publications (22)50.01 Total impact

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    ABSTRACT: Pulmonary hypertension is a progressive disease characterized by marked pulmonary arterial remodeling and increased vascular resistance. Inflammation and oxidative stress promote the development of pulmonary hypertension. Oxymatrine, one of the main active components of Chinese herb Sophora flavescens Ait (Kushen), plays anti-inflammatory and antioxidant protective roles, which effects on pulmonary arteries remain unclear. The present study aimed to investigate the effects of oxymatrine on pulmonary hypertension development. Sprague-Dawley rats were exposed to hypoxia for 28 days or injected with monocrotaline to develop pulmonary hypertension along with administration of oxymatrine (50mg/kg/day). Hemodynamics and pulmonary arterial remodeling data of rats were then obtained. The anti-proliferation effect of oxymatrine was verified by in vitro assays. The inflammatory cytokines' mRNA levels and the leukocytes and T cells accumulation in lung tissue were detected. The anti-oxidative effects of oxymatrine were explored in vitro. Our study showed that oxymatrine treatment attenuated right ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia or monocrotaline, inhibited proliferation of pulmonary arterial smooth muscle cells(PASMCs). Increased expression of inflammatory cytokines in mRNA and accumulation of leukocytes and T cells around the pulmonary arteries were suppressed with oxymatrine administration. Under hypoxic condition, oxymatrine significantly up-regulated Nrf2 and antioxidant protein SOD1 and HO-1 expression, but down-regulated hydroperoxides level in PASMCs. In summary, the present study indicated that oxymatrine may prevent pulmonary hypertension through its anti-proliferative, anti-inflammatory and antioxidant effects, thus providing a promising pharmacological perspective for treating pulmonary hypertension.
    Free Radical Biology & Medicine 01/2014; · 5.27 Impact Factor
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    ABSTRACT: Inflammation and pulmonary edema are involved in the pathogenesis of seawater aspiration-induced acute lung injury (ALI). Although several studies have reported that 1α,25-Dihydroxyvitamin D3 (calcitriol) suppresses inflammation, it has not been confirmed to be effective in seawater aspiration-induced ALI. Thus, we investigated the effect of calcitriol on seawater aspiration-induced ALI and explored the probable mechanism.
    PLoS ONE 01/2014; 9(8):e104507. · 3.73 Impact Factor
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    ABSTRACT: Leptin is reported to be involved in acute lung injury (ALI). However, the role and underlying mechanisms of leptin in ALI remain unclear. The aim of this study was to determine whether leptin deficiency promoted the development of acute lung injury. Lipopolysaccharide (LPS) or oleic acid(OA) were administered to wild-type and leptin deficient (ob/ob) mice to induce ALI. Leptin level, survival rate and lung injury were examined. Results showed that leptin levels were predominantly increased in the lung, but also in the heart, liver, kidney and adipose tissue after LPS adminiatration. Compared with wild-type mice, LPS or OA-induced lung injury was worse and the survival rate was lower in ob/ob mice. Moreover, leptin deficiency promoted the release of proinflammatory cytokines. Exogenous administration of leptin reduced lethality in ob/ob mice and ameliorated lung injury partly through inhibiting the activation of NF-κB, p38 and ERK pathways. These results indicated that leptin deficiency contributed to the development of lung injury by enhancing inflammatory response and high level of leptin improved survival and protected against ALI.
    American Journal of Respiratory Cell and Molecular Biology 07/2013; · 4.15 Impact Factor
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    ABSTRACT: We previously showed that tanshinone IIA ameliorated the hypoxia-induced pulmonary hypertension (HPH) partially by attenuating pulmonary artery remodeling. The hypoxia-induced proliferation of pulmonary artery smooth muscle cells (PASMCs) is one of the major causes for pulmonary arterial remodeling, therefore the present study was performed to explore the effects and underlying mechanism of tanshinone IIA on the hypoxia-induced PASMCs proliferation. PASMCs were isolated from male Sprague-Dawley rats and cultured in normoxic (21%) or hypoxic (3%) condition. Cell proliferation was measured with 3 - (4, 5 - dimethylthiazal - 2 - yl) - 2, 5 - diphenyltetrazoliumbromide assay and cell counting. Cell cycle was measured with flow cytometry. The expression of of p27, Skp-2 and the phosphorylation of Akt were measured using western blot and/or RT-PCR respectively. The results showed that tanshinone IIA significantly inhibited the hypoxia-induced PASMCs proliferation in a concentration-dependent manner and arrested the cells in G1/G0-phase. Tanshinone IIA reversed the hypoxia-induced reduction of p27 protein, a cyclin-dependent kinase inhibitor, in PASMCs by slowing down its degradation. Knockdown of p27 with specific siRNA abolished the anti-proliferation of tanshinone IIA. Moreover, tanshinone IIA inhibited the hypoxia-induced increase of S-phase kinase-associated protein 2 (Skp2) and the phosphorylation of Akt, both of which are involved in the degradation of p27 protein. In vivo tanshinone IIA significantly upregulated the hypoxia-induced p27 protein reduction and downregulated the hypoxia-induced Skp2 increase in pulmonary arteries in HPH rats. Therefore, we propose that the inhibition of tanshinone IIA on hypoxia-induce PASMCs proliferation may be due to arresting the cells in G1/G0-phase by slowing down the hypoxia-induced degradation of p27 via Akt/Skp2-associated pathway. The novel information partially explained the anti-remodeling property of tanshinone IIA on pulmonary artery in HPH.
    PLoS ONE 01/2013; 8(2):e56774. · 3.73 Impact Factor
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    ABSTRACT: Exogenous estrogen was shown to exert various beneficial effects on multiple diseases including hypoxia-induced pulmonary hypertension (HPH). However, the effect of endogenous estrogen on HPH was seldom investigated. In the present study, we explored the protective effects and mechanisms of endogenous estrogen on hypoxia-induced pulmonary hypertension. Male, female, pregnant and ovariectomized rats were housed in a hypoxic condition for 21 days, and then hemodynamic together with morphologic indexes of pulmonary circulation were measured. The right ventricular systolic pressure, mean pulmonary artery pressure, right ventricular hypertrophy index, and arterial remodeling index were significantly elevated after chronic hypoxia exposure. Experimental data showed less severity in female, especially in pregnant rats. In vitro, artery rings of different sex or estrus cycle rats were obtained, and then artery rings experiments were performed to investigate pulmonary vasoconstriction by recording the maximum phase II vasoconstriction. Data showed that the vasoconstriction was milder in proestrus female than diestrus female or male groups, which could be leveled by treating U0126 (a MAPK pathway inhibitor). Pulmonary arterial smooth muscle cells isolated from different sex or estrus cycle rats were cultured in the condition of 2% oxygen for 24 hours, and cell proliferation was evaluated by the [3H]-thymidine incorporation assay. Cells from proestrus rats exhibited lower proliferation than the other groups, which could be countered by both U0126 and raloxifene (a selective estrogen receptor modulator). Serum estradiol levels were detected, and rats with higher levels showed less severity of pulmonary hypertension. Conclusively, endogenous estrogen may alleviate hypoxia-induced pulmonary hypertension by attenuating vasoconstriction through non-genomic mechanisms and inhibiting smooth muscle cells proliferation through both genomic and non-genomic mechanisms.
    International journal of medical sciences 01/2013; 10(6):771-81. · 2.07 Impact Factor
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    ABSTRACT: Alveolar macrophages (AMs) play a vital role in lung immunity. The recent studies demonstrated that potassium channels were associated with macrophage functions, such as activation, migration and cytokines secretion. However, less is known regarding the expression and function of ERG channels in AMs. Our study showed that ERG1 channel expressed in rat alveolar macrophage, and the expression level was increased when AMs were stimulated with LPS. Furthermore, blockade of ERG1 channels with E4031 down-regulated the mature of ERG1 protein, inhibited NF-κB translocation into the nucleus, and reduced LPS-stimulated IL-6 and IL-1β secretion. These results imply that ERG1 channels are functionally expressed in rat alveolar macrophages and play an important role in inflammatory response.
    Journal of molecular histology 11/2012; · 1.75 Impact Factor
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    ABSTRACT: Our previous study showed that seawater can cause lung tissue cell apoptosis; in the present study, the immunohistochemistry and Western blot analysis results demonstrated that Fas, FasL, and cleaved caspase-8 and caspase-3 were up-regulated in the rat lungs exposed to seawater. We found that seawater-induced human lung alveolar epithelial A549 cell apoptosis was concentration and time dependent. Moreover, seawater increased the expression of Fas, FasL, and cleaved caspase-8 and caspase-3 in A549 cells. The incubation of A549 cells in the presence of FasL-neutralising antibody (NOK-2) or caspase-8 inhibitor (Z-IETD-FMK) resulted in a decrease of seawater-induced cell apoptosis. NOK-2 inhibited Fas/FasL interaction and reduced the cleavage of caspase-8 and caspase-3, and Z-IETD-FMK blocked caspase-8 and caspase-3 activation. Seawater similarly produced a significant increase in rat alveolar type II cell apoptosis and expression of Fas and cleaved caspase-8. In summary, the Fas/FasL pathway involved in alveolar epithelial cell (AEC) apoptosis could be important in the pathogenesis of seawater-induced acute lung injury (SW-ALI).
    Respiratory Physiology & Neurobiology 05/2012; 182(2-3):71-80. · 2.05 Impact Factor
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    ABSTRACT: Hypoxic pulmonary vasoconstriction may lead to pulmonary hypertension, but the underlying mechanisms of persistent vasoconstriction are still unclear. There is evidence that pulmonary inflammation contributes to the abnormalities of function in the pulmonary artery (PA) following chronic hypoxia exposure. Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine, and we found that expression of MIF was increased in the smooth muscle of PA from hypoxic pulmonary hypertensive rats. Therefore, the aim of the study was to investigate the role of MIF in modulating vasoreactivity of isolated PA rings. Sprague-Dawley rats were challenged by intermittent chronic hypoxia exposure for 4 weeks to establish hypoxic pulmonary hypertension models. Subsequently, immunohistochemistry and western blot assay were used to examine the MIF expression in pulmonary artery. Moreover, isometric force displacement was measured in isolated intrapulmonary artery. In the isolated PA, our results showed that MIF mediated the enhanced pulmonary arterial vasoconstriction in response to chronic hypoxia, and the delayed hypoxic constriction in a biphasic pattern of constriction occurs in response to acute hypoxia. We also present the finding that MIF had no effect on force on its own, but concentration-dependently potentiated constrictions pre-evoked by phenylephrine under normoxic condition. The potentiation was independent of the endothelium. MIF-induced potentiation of phenylephrine-evoked constriction was partially inhibited by PKC inhibitor chelerythrine, p38 inhibitor SB 203580, ERK1/2 inhibitor U0126, respectively. Our results suggested that MIF enhanced vasoconstriction of pulmonary artery elicited by agonist through PKC, p38 and ERK1/2 signal pathways, which may contributes to hypoxic pulmonary vasoconstriction.
    Microvascular Research 03/2012; 83(2):205-12. · 2.93 Impact Factor
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    ABSTRACT: Pulmonary hypertension (PH) contributes to the mortality of patients with lung and heart diseases. However, the underlying mechanism has not been completely elucidated. Accumulating evidence suggests that inflammatory response may be involved in the pathogenesis of PH. Macrophage migration inhibitory factor (MIF) is a critical upstream inflammatory mediator which promotes a broad range of pathophysiological processes. The aim of the study was to investigate the role of MIF in the pulmonary vascular remodeling of hypoxia-induced PH. We found that MIF mRNA and protein expression was increased in the lung tissues from hypoxic pulmonary hypertensive rats. Intensive immunoreactivity for MIF was observed in smooth muscle cells of large pulmonary arteries (PAs), endothelial cells of small PAs, and inflammatory cells of hypoxic lungs. MIF participated in the hypoxia-induced PASMCs proliferation, and it could directly stimulate proliferation of these cells. MIF-induced enhanced growth of PASMCs was attenuated by MEK and JNK inhibitor. Besides, MIF antagonist ISO-1 suppressed the ERK1/2 and JNK phosphorylation induced by MIF. In conclusion, the current finding suggested that MIF may act on the proliferation of PASMCs through the activation of the ERK1/2 and JNK pathways, which contributes to hypoxic pulmonary hypertension.
    Mediators of Inflammation 01/2012; 2012:840737. · 3.88 Impact Factor
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    ABSTRACT: Matrine is one of the main active components of Chinese herb Sophora flavescens Ait (Kushen), which has been demonstrated to be effective in suppressing inflammation. The aim of the present study is to investigate the effect of matrine on LPS-induced lung injury. Lung injury was assessed by histological study and wet to dry weight ratios, as well as cell count and protein content in bronchoalveolar lavage fluid. We also detected MPO activity reflecting neutrophil infiltration and MDA activity examining oxidative stress in lung tissues. Cytokines and ROS production in cells were monitored by ELISA and flow cytometry, respectively. The results showed that high dose of matrine significantly reduced the mortality rate of mice with LPS administration. Treatment with matrine improved LPS-induced lung histopathologic changes, alleviated pulmonary edema and lung vascular leak, inhibited MPO and MDA activity,and reduced the production of inflammatory mediators including TNF-α, IL-6 and HMGB1. In vitro, matrine administration reduced the production of ROS and inflammatory factors, which was possibly associated with inhibition of NF-κB. In conclusion, the current study demonstrated that matrine exhibited a protective effect on LPS-induced acute lung injury by inhibiting of the inflammatory response, which may involve the suppression of ROS and tissue oxidative stress.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 12/2011; 44(5):573-9. · 2.61 Impact Factor
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    ABSTRACT: 1. Smooth muscle progenitor cells (SPC) are undifferentiated vascular smooth muscle cells implicated in many hyperplastic diseases of the blood vessels. However, few in vitro studies have investigated the characteristics of SPC. 2. In the present study, we constructed a recombinant plasmid with the enhanced green fluorescent protein (GFP) gene and a rat SM22α promoter, which was exclusively promoted in a smooth muscle cell lineage. Constructs were then transferred into adherent mononuclear cells derived from rat bone marrow. After 3 days, GFP-positive cells, which should be SPC, were isolated by flow cytometry. 3. Flow cytometric analysis and dual immunofluorescent staining showed that the GFP-positive cells expressed both α-smooth muscle actin (a specific marker for smooth muscle) and the chemokine receptor CXCR4 (abundant on precursor cells), but not calmodulin or CD31. After stimulation of SPC with 50 ng/mL platelet-derived growth factor-BB, CXCR4 levels decreased and calmodulin protein content increased, as determined by western blot analysis. 4. On the basis of these results, we conclude that SPC have dual characteristics of both precursor and smooth muscle cells, and might well differentiate into smooth muscle-like cells under certain conditions.
    Clinical and Experimental Pharmacology and Physiology 06/2011; 38(9):586-91. · 2.41 Impact Factor
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    ABSTRACT: Bicyclol is synthesized based on schisandrin, which is one of the main active components of Chinese herb Fructus Schisandrae. The purpose of this study is to investigate whether bicyclol has a beneficial effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Bicyclol was given to mice by gavage for three times. ALI was induced by vena caudalis injection of LPS. The last dose of bicyclol was administrated 1 h before LPS given. Mice in each group were sacrificed at different time point after LPS administration. As revealed by survival study, pretreatment with high doses of bicyclol reduced the mortality of mice from ALI. Bicyclol pretreatment significantly improved LPS-induced lung pathological changes, inhibited myeloperoxidase (MPO) activity, and reduced lung/body and lung wet/dry weight ratios. Bicyclol also inhibited the release of TNF-α, IL-1β and HMGB1, whereas simultaneously increased the expression of IL-10. Furthermore, the phosphorylation level of NF-κB p65 was markedly decreased by bicyclol. Taken together, our study showed that bicyclol improves survival rate and attenuates LPS-induced ALI. The protective mechanism may be due to the inhibition of NF-κB activation and regulation of cytokine secretion.
    Pulmonary Pharmacology &amp Therapeutics 01/2011; 24(2):240-6. · 2.54 Impact Factor
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    ABSTRACT: The present study was designed to investigate the vascular effects and underlying mechanisms of tanshinone IIA on isolated rat pulmonary artery. Isometric tension was recorded in the arteries from normal and hypoxic pulmonary hypertension rats under normoxia or hypoxia condition. The results showed that tanshinone IIA exerted a biphasic effect on rat pulmonary artery. The constriction was attenuated by endothelium-denudation but was enhanced by inhibition of nitric oxide synthase. Pretreatment with tetraethylammonium (Ca2+-activated K+ channel inhibitor) upward shifted the concentration-response curve without affecting the maximum dilatation. Pretreatment with zinc protoporphyrin IX (heme oxygenase-1 inhibitor), 4-aminopyridine (KV channel inhibitor), glibenclamide (KATP channel inhibitor) or BaCl2 (inwardly rectifying K+ channel inhibitor) did not affect the vasoreactivity. Meanwhile, tanshinone IIA almost abolished vasoconstriction induced by extracellular Ca2+. Under hypoxia condition, tanshinone IIA eliminated acute hypoxia-induced initial contraction, potentiated following vasorelaxation, attenuated and reversed sustained contraction to relaxation in pulmonary artery from normal rats, and reversed phenylephrine-induced sustained constriction to sustained relaxation in remodeled pulmonary artery from hypoxic pulmonary hypertension rats. We concluded that the mild constrictive effect induced by tanshinone IIA was affected by integrity of endothelium and production of nitric oxide, while the potent dilative effect was endothelium-independent and produced primarily by inhibiting extracellular Ca2+ influx and partially by inhibiting intracellular Ca2+ release, as well as activating Ca2+-activated K+ channels. The modulation of tanshinone IIA on pulmonary vasoreactivity under both acute and chronic hypoxia condition may provide a new insight for curing hypoxic pulmonary hypertension.
    European journal of pharmacology 05/2010; 640(1-3):129-38. · 2.59 Impact Factor
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    ABSTRACT: Chronic hypoxia results in pulmonary hypertension. To investigate the role of Na+/H+ exchange in this process, we determined the effect of amiloride, a Na+/H+ exchange inhibitor, on hypoxic pulmonary hypertension and pulmonary arterial smooth muscle cell proliferation, both in vivo and in vitro. Sprague-Dawley rats were placed either in a hypobaric, hypoxic chamber (10.5% 02) or under normal 21% O2 atmosphere for 8 h each day for 3 weeks. Rats under hypoxic conditions received 1, 3, or 10 mg/kg/d amiloride or the vehicle alone. Hematologic indices, including red blood cells, hemoglobin, hematocrit and mean corpuscular hemoglobin increased in hypoxic rats, but these changes were prevented by treatment with amiloride. In the hypoxic rats, the right ventricular systolic pressure and right ventricular hypertension index (weight ratio of right ventricular to left and septum together) were increased by 88% and 129%, respectively. Arteriolar wall thickness and area in the hypoxia-treated animals increased 3- and 2-fold, respectively, over normoxic controls; the increase in each of these indices was attenuated by amiloride in a dose-dependent manner. In cultured pulmonary arterial smooth muscle cells, hypoxia greatly increased cellular proliferation, and this similarly showed a dose-dependent attenuation in the presence of amiloride. Amiloride did not affect blood pressure in vivo or cause cell damage in vitro. These data suggest that the Na+/H+ exchange inhibitor amiloride may represent an effective adjunctive therapy in pulmonary hypertension induced by chronic hypoxia.
    The Chinese journal of physiology 02/2010; 53(1):36-44. · 0.75 Impact Factor
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    ABSTRACT: Pulmonary vascular structure remodeling (PVSR) is a hallmark of pulmonary hypertension. P27(kip1), one of critical cyclin-dependent kinase inhibitors, has been shown to mediate anti-proliferation effects on various vascular cells. Beta-estradiol (β-E2) has numerous biological protective effects including attenuation of hypoxic pulmonary hypertension (HPH). In the present study, we employed β-E2 to investigate the roles of p27(kip1) and its closely-related kinase (Skp-2) in the progression of PVSR and HPH. Sprague-Dawley rats treated with or without β-E2 were challenged by intermittent chronic hypoxia exposure for 4 weeks to establish hypoxic pulmonary hypertension models, which resemble moderate severity of hypoxia-induced PH in humans. Subsequently, hemodynamic and pulmonary pathomorphology data were gathered. Additionally, pulmonary artery smooth muscle cells (PASMCs) were cultured to determine the anti-proliferation effect of β-E2 under hypoxia exposure. Western blotting or reverse transcriptional polymerase chain reaction (RT-PCR) were adopted to test p27(kip1), Skp-2 and Akt-P changes in rat lung tissue and cultured PASMCs. Chronic hypoxia significantly increased right ventricular systolic pressures (RVSP), weight of right ventricle/left ventricle plus septum (RV/LV+S) ratio, medial width of pulmonary arterioles, accompanied with decreased expression of p27(kip1) in rats. Whereas, β-E2 treatment repressed the elevation of RVSP, RV/LV+S, attenuated the PVSR of pulmonary arterioles induced by chronic hypoxia, and stabilized the expression of p27(kip1). Study also showed that β-E2 application suppressed the proliferation of PASMCs and elevated the expression of p27(kip1) under hypoxia exposure. In addition, experiments both in vivo and in vitro consistently indicated an escalation of Skp-2 and phosphorylated Akt under hypoxia condition. Besides, all these changes were alleviated in the presence of β-E2. Our results suggest that β-E2 can effectively attenuate PVSR and HPH. The underlying mechanism may partially be through the increased p27(kip1) by inhibiting Skp-2 through Akt signal pathway. Therefore, targeting up-regulation of p27(kip1) or down-regulation of Skp-2 might provide new strategies for treatment of HPH.
    Respiratory research 01/2010; 11:182. · 3.64 Impact Factor
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    European Journal of Pharmacology. 06/2009; 611(s 1–3):107.
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    ABSTRACT: Tanshinone IIA (TIIA) is one of the main active components from Chinese herb danshen. Previous reports showed that TIIA reduced the production of pro-inflammatory mediators stimulated with lipopolysaccharide (LPS). However, the effects of TIIA on LPS-induced acute lung injury are not fully understood. Here, we observed the effects of TIIA on mortality and lung injury in LPS-treated mice and on LPS-induced pulmonary epithelial cell injury, and further studied the underlying mechanism. As revealed by survival study, pretreatment with TIIA reduced mortality of mice and prolonged their survival time. Meanwhile, TIIA pretreatment significantly improved LPS-induced lung histopathologic changes, decreased lung wet-to-dry and lung-to-body weight ratios, inhibited lung myeloperoxidase activity and reduced protein leakage. TIIA also alleviated LPS-induced pulmonary epithelial cell injury, as proved by methyl thiazolyl tetrazolium (MTT) and lactic dehydrogenase assay. Furthermore, TIIA suppressed LPS-induced phospholipase A2 (PLA2) activity in both lung homogenate and bronchoalveolar lavage fluid. TIIA also inhibited the metabolites of PLA2, which was confirmed by results of thromboxane B2, prostaglandin E2 and leukotriene B4 detection. Besides, TIIA in vitro inhibited LPS-induced PLA2 activity in a dose-dependent manner. Western blotting showed that TIIA markedly inhibited the activation of nuclear factor kappa B (NF-kappaB) in LPS-treated mice. Taken together, these data firstly provided the novel information that the protective role of TIIA against LPS-induced lung injury may attribute partly to the inhibition of PLA2 activity and NF-kappaB activation.
    European journal of pharmacology 05/2009; 607(1-3):194-200. · 2.59 Impact Factor
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    ABSTRACT: In the present study we reported the expression of the 5-HT2C receptor (5-HT2C-R) in the aorta and the pulmonary artery in rats exposed to hypoxia, and examined its role in vascular smooth muscle cells. Immunochemistry, quantitative RT-PCR, and western blot were used to examine 5-HT2C-R expression. Small interfering RNA (siRNA) was used to explore the role of 5-HT2C-R in vascular smooth muscle cells proliferation and contraction induced by 5-HT.5-HT2C-R immunoreactivity was confined predominantly to the plasma membrane in the rat aortic smooth muscle cells (ASMCs) and the pulmonary arterial smooth muscle cells (PASMCs). 5-HT2C-R mRNA expression in the aorta of hypoxic pulmonary hypertension (HPH) rats was more than that in the pulmonary artery. Hypoxia-induced 5-HT2C-R protein expression in the aorta was less than that in the pulmonary artery, indicating that 5-HT2C-R might mediate different responses of the aorta and the pulmonary artery to 5-HT in HPH. We also demonstrated that RNA editing may not be involved in the different expression levels of 5-HT2C-R in the aorta and the pulmonary artery. The higher expression of 5-HT2C-R in the pulmonary artery versus the aorta of HPH rats was partly due to the increased protein stability. siRNA was used to knock down the expression of 5-HT2C-R. 5-HT2C-R-specific siRNA reduced the proliferation and contraction of vascular smooth muscle cells induced by 5-HT. In conclusion, the different expression patterns of 5-HT2C-R protein in the aorta and the pulmonary artery suggest that this 5-HT receptor may be involved, at least partly, in modulating different responses of systemic vessels and pulmonary vasculature to 5-HT in HPH.
    The Chinese journal of physiology 01/2009; 51(6):338-47. · 0.75 Impact Factor
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    ABSTRACT: Tanshinone IIA, one of the main active components from Chinese herb Danshen, is widely used to treat cardiovascular diseases including arrhythmia in Asian countries especially in China. However, the mechanisms underlying its anti-arrythmia effects are not clear. In this study we investigate the effects of tanshinone IIA on human KCNQ1/KCNE1 potassium channels (I(Ks)), human ether-a-go-go-related gene potassium channels (hERG), Kv1.5 potassium channels, inward rectifier potassium channels (I(K1)) expressed in HEK 293 cells using patch clamp technique. Tanshinone IIA potently and reversibly enhanced the amplitude of I(Ks) in a concentration dependent manner with an EC(50) of 64.5 microM, accelerated the activation rate of I(Ks) channels, decelerated their deactivation and shifted the voltage dependence of I(Ks) activation to negative direction. Isoproteronol, a stimulator of beta-adrenergic receptor, at 1 microM and sodium nitroprusside (SNP), a NO donor, at 1 mM, had no significant effects on the enhancement of I(Ks) by 30 microM tanshinone IIA. N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), a selective protein kinase A inhibitor, at 0.1 microM and 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one (ODQ), a selective nitric oxide-sensitive guanylyl cyclase inhibitor, at 10 microM, also had no significant effects on the enhancement of I(Ks) by 30 microM tanshinone IIA. Tanshinone IIA did not affect expressed hERG channels, Kv1.5 channels and I(K1) channels. These results indicate that tanshinone IIA directly and specifically activate human cardiac KCNQ1/KCNE1 potassium channels (I(Ks)) in HEK 293 cell through affecting the channels' kinetics.
    European Journal of Pharmacology 07/2008; 590(1-3):317-21. · 2.59 Impact Factor
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    ABSTRACT: To study the influence of Na+/H+ exchange inhibitor amiloride on hypoxia-induced proliferation in rats pulmonary artery smooth muscle cells (PASMCs), also observe the change of Na+/H+ exchanger-1 (NHE-1) activity and expression. Rats PASMGs were cultured in normoxia (21% O2) or hypoxia (2%O2) for 24 hours, as well as administered amiloride with various concentrations, cultured for 24 hours, then determined MTT OD values and rates of PCNA positive cells to investigate cells proliferation, moreover intracellular pH was determined by interactive Laser Cytometer, and Na+/H+ exchanger-1 mRNA expression was determined by RT-PCR. Hypoxic exposure heightened intracellular pH and mRNA expression of NHE-1 in PASMCs, however, 3.123-50 micromol/L amiloride depressed them gradually. Additionally, hypoxic exposure raised MTT OD value and rates of PCNA positive cells, similarly, the above two indexes descended gradually with presence of 3.125-50 micromol/L amiloride. Na+/H+ exchange inhibitor amiloride can suppress hypoxia-induced proliferation in pulmonary artery smooth muscle cells, which is due to depress activity and expression of NHE-1.
    Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology 11/2007; 23(4):462-5.