关键词: 毒蕈碱受体亚型3, 低氧损伤, 低氧诱导因子-1α, 血红素加氧酶-1

Abstract: Objective To investigate the cytoprotection and mechanism of carbachol(CCH) stimulate M3 muscarinic acetylcholine receptor(M3-mAChR) against on hypoxia injury induced by Cobaltous chloride hexahydrate(CoCl2) in rat cardiomyocyte strain H9c2. Methods Select the normal rat cardiomyocyte strain H9c2 as the control group, rat cardiomyocyte strain H9c2 were managed with CoCl2 to establish hypoxia injury model, M3-mAChR specific agonist CCH and antagonist 4-diphenyl-acetoxy-N-methyl-piperidine methiodide(4-DAMP) were used for intervention. The cell viability was tested by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT); The apoptosis in cardiomyocyte was detected by flow cytomery(FCM); The expression levels of M3-mAChR, caspase-3, HIF-1α and HO-1 proteins were measured by Western blot assay. Results In hypoxia group, the apoptosis rate was significantly increased, cell proliferation was distinctly decreased, and the expression of HIF-1α, caspase-3 and HO-1 proteins were up-regulated obviously; After treated with CCH, the apoptosis rate of cardiomyocytes was significantly decreased, while the proliferation of cells was significantly increased, and the expression of M3-mAChR, HIF-1α and HO-1 proteins were increased, and the expression of caspase-3 protein was significantly decreased. Moreover, when applying 4-DAMP for intervention, these effects that mediated by CCH was abolished. Conclusions CCH stimulate M3-mAChR against on hypoxia injury induced by CoCl2 in rat cardiomyocyte strain H9c2, and the mechanism may be related to down-regulation of caspase-3 expression and up-regulation of HIF-1α and HO-1 protein expression.

Key words: M3-mAChR, hypoxia injury, HIF-1α, HO-1