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Shi Y.P.,Thadweik Academy of Medicine
Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology | Year: 2013

To investigate the protective effects of Shengui tablet (Chinese Traditional Medicine) on experimental cerebral ischemia by acute cerebral ischemia hypoxia in mice and bilateral ligation of the carotid artery in rats. In the acute cerebral ischemia hypoxia model, the mice were randomly divided into control group, low-, middle- and high-dose (0.16, 0.33 and 1.00 g/kg) groups of Shengui tablet, after oral treatment for 30 d, gasping time of isolated heads of mice were observed. In bilateral ligation of the carotid artery cerebral ischemia model, the rats were randomly divided into control group, model group and low-, middle-, high-dose (0.072, 0.149 and 0.450 g/kg) groups of Shengui tablet. After oral treatment for 7 d, the cerebral index, superoxide dismutase (SOD) activity and the content of malondialdehyde (MDA) were measured. Compared with the control model, Shengui tablet middle- and high-dose could significantly prolong gasping time of isolate heads of mice. Compared with model group, Shengui tablet low-, middle- and high-dose could significantly decrease the cerebral index and enhance SOD activity in brain tissue; only high-dose could reduce the content of MDA. Shengui tablet has significant protective effect on the cerebral ischemia. Source


Zhao R.-J.,Academy of Military Medical Science | Wang H.,Academy of Military Medical Science | Wang H.,Thadweik Academy of Medicine
Acta Pharmacologica Sinica | Year: 2011

Aim: To elucidate the modulation of the chemerin/ChemR23 axis by iptakalim-induced opening of KATP channels and to determine the role of the chemerin/ChemR23 axis in the iptakalim-mediated endothelial protection. Methods: Cultured rat aortic endothelial cells (RAECs) were used. Chemerin secretion and ChemR23 protein expression were investigated using Western blot analysis. The gene expression level of ChemR23 was examined with RT-PCR. In addition, the release of nitric oxide (NO) was measured with a nitric oxide assay. Results: Homocysteine, uric acid, high glucose, or oxidized low-density lipoprotein (ox-LDL) down-regulated the chemerin secretion and ChemR23 gene/protein expression in RAECs as a function of concentration and time, which was reversed by pretreatment with iptakalim (1-10 μmol/L). Moreover, these effects of iptakalim were abolished in the presence of the KATP channel antagonist glibenclamide (1 μmol/L). Both iptakalim and recombinant chemerin restored the impaired NO production in RAECs induced by uric acid, and the effects were abolished by anti-ChemR23 antibodies. Conclusion: Iptakalim via opening KATP channels enhanced the endothelial chemerin/ChemR23 axis and NO production, thus improving endothelial function. © 2011 CPS and SIMM All rights reserved. Source


Duan R.-F.,Academy of Military Medical Science | Cui W.-Y.,Academy of Military Medical Science | Wang H.,Academy of Military Medical Science | Wang H.,Thadweik Academy of Medicine
Acta Pharmacologica Sinica | Year: 2011

Aim: To study the relationship between the antihypertensive response of iptakalim and KCNJ11 polymorphisms in Chinese Han hypertensive patients. Methods: One hundred sixty two Chinese Han hypertensive patients were administered iptakalim (5 or 10 mg/d, po) for 8 weeks. Before the treatment and 24 h after completing the treatment blood pressure (BP) was measured. Genotyping was performed using direct sequencing. Results: Four common A190A, E23K, I337V and 3′UTR +62 G/A polymorphisms were found in KCNJ11. The E23K, I337V and 3′UTR +62 G/A polymorphisms were in complete linkage disequilibrium, and I337V was used as a representative. There were no significant differences in age, body mass index, sex, baseline systolic BP (SBP) and diastolic BP (DBP) among the 3 genotypes for the four polymorphisms. Significant association was found between SBP response and the polymorphisms (adjusted regression coefficient: 3.5 [1.2] mmHg; P=0.003 for the A190A polymorphism; adjusted regression coefficient: 3.1 [1.2] mmHg; P=0.012 for the I337V polymorphism). The patients with TT genotype for A190A polymorphism had higher clinical efficacy than those with CC genotype. Conclusion: The results suggest the KCNJ11 polymorphisms are associated with the SBP-lowering response of short-term iptakalim therapy in Chinese Han hypertensive patients. © 2011 CPS and SIMM All rights reserved. Source


Ran Y.-H.,Academy of Military Medical Science | Wang H.,Academy of Military Medical Science | Wang H.,Thadweik Academy of Medicine
Journal of Zhejiang University: Science B | Year: 2011

Objective: To investigate the role of iptakalim, an ATP-sensitive potassium channel opener, in transient cerebral ischemia/reperfusion (I/R) injury and its involved mechanisms. Methods: Intraluminal occlusion of middle cerebral artery (MCAO) in a rat model was used to investigate the effect of iptakalim at different time points. Infarct volume was measured by staining with 2,3,5-triphenyltetrazolium chloride, and immunohistochemistry was used to evaluate the expressions of Bcl-2 and Bax. In vitro, neurovascular unit (NVU) cells, including rat primary cortical neurons, astrocytes, and cerebral microvascular endothelial cells, were cultured and underwent oxygen-glucose deprivation (OGD). The protective effect of iptakalim on NVU cells was investigated by cell viability and injury assessments, which were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and release of lactate dehydrogenase. Caspase-3, Bcl-2 and Bax mRNA expressions were evaluated by real-time polymerase chain reaction (PCR). Results: Administration of iptakalim 0 or 1 h after reperfusion significantly reduced infarct volumes, improved neurological scores, and attenuated brain edema after cerebral I/R injury. Iptakalim treatment (0 h after reperfusion) also reduced caspase-3 expression and increased the ratio of Bcl-2 to Bax by immunohistochemistry. Iptakalim inhibited OGD-induced cell death in cultured neurons and astrocytes, and lactate dehydrogenase release from cerebral microvascular endothelial cells. Iptakalim reduced mRNA expression of caspase-3 and increased the ratio of Bcl-2 to Bax in NVU cells. Conclusions: Iptakalim confers neuroprotection against cerebral I/R injury by protecting NVU cells via inhibiting of apoptosis. © 2011 Zhejiang University and Springer-Verlag Berlin Heidelberg. Source


Zhao R.-J.,Academy of Military Medical Science | Pan Z.-Y.,Academy of Military Medical Science | Long C.-L.,Academy of Military Medical Science | Cui W.-Y.,Academy of Military Medical Science | And 3 more authors.
Life Sciences | Year: 2013

Aims Endothelial cells play a pivotal role in vascular intimal inflammation during cardiovascular diseases. The chemerin/ChemR23 system in endothelial cells is one of physiological mechanisms that regulate inflammatory responses. Our previous studies indicated that stimulation of non-neuronal muscarinic receptor (NNMR) improved endothelial dysfunction. However, the relationship between the chemerin/ChemR23 signaling axis and NNMR in endothelial cell is poorly understood. Here, we first investigated whether the modulation of chemerin/ChemR23 signaling axis is involved in NNMR-mediated endothelial protection. Main methods Cultured rat aortic endothelial cells (RAECs) were used. The ChemR23 protein expression and chemerin secretion were measured using Western blot analysis. The gene expression level of ChemR23 was examined with reverse transcriptase PCR (RT-PCR). The production of nitric oxide (NO) was determined by a nitrate reductase assay kit. Key findings A sharp decline of chemerin secretion and ChemR23 protein/gene expression was observed in RAECs after exposed to homocysteine at concentration of 0.5 mmol/L. Arecoline (10 μmol/L) pretreatment increased ChemR23 protein expression as well as mRNA expression, and enhanced the secretion of chemerin. Arecoline could also reverse the decreased ChemR23 mRNA expression induced by uric acid, high glucose, or oxidized low-density lipoprotein. Furthermore, the modulation of arecoline on chemerin/ChemR23 signaling axis was absolutely abolished in the presence of the nonselective muscarinic receptors antagonist atropine 1 μmol/L. Additionally, arecoline improved endothelial dysfunction by increasing the reduced NO production induced by uric acid, which was blocked by anti-ChemR23 antibody. Significance The chemerin/ChemR23 signaling axis participates in NNMR-mediated protection against endothelial dysfunction in cardiovascular system. © 2012 Elsevier Inc. All rights reserved. Source

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