缬沙坦抑制缺氧时肥大心肌细胞凋亡及Cx43表达下调

Valsartan Block Down-Regulation of Cx43 Protein and Apoptosis of Hypertrophic Cadiocytes in Hypoxia Conditions

目的探讨缬沙坦对缺氧环境下肥大心肌细胞缝隙连接蛋白Cx43表达的影响。方法培养心肌细胞或在诱导肥大后分别缺氧24h,采用免疫荧光方法和Western-blot法分别检测缝隙连接蛋白Cx43总蛋白表达变化,同时观察缬沙坦对缺氧状态下肥大心肌细胞Cx43表达的影响。结果缺氧24h后可致正常心肌细胞Cx43表达下调13%(P<0.01),心肌细胞经血管紧张素Ⅱ诱导48h后可出现肥大,而肥大心肌细胞比正常心肌细胞在缺氧24h后Cx43总蛋白表达显示出更明显的下调(P<0.01),缬沙坦可抑制缺氧状态下肥大心肌细胞的凋亡和Cx43总蛋白表达的下调。结论缺氧可导致心肌细胞Cx43表达下调,而肥大心肌细胞在缺氧时总蛋白下调更为明显,而缬沙坦可部分抑制肥大心肌细胞缺氧时的凋亡和Cx43总蛋白下调,这可能与缬沙坦改善缺氧时肥大心肌的电生理重构和恶性心律失常的机制有关。

Objective To investigate the effects of Valsartan on the expression of Cx43 in hypertrophic cardiocytes in hypoxia conditions.Methods Cardiac muscle cells from newly born rats（1-3 d） and induced hypertrophic cardiocytes were cultured in hypoxia conditions.After 24 h,the expression of total Cx43 protein were detected by western-blot or fluorescent staining method.Valsartan was tested to observe the its effects on the expression of Cx43 in hypertrophic cardiocytes in hypoxia conditions.Results Hypoxia of 24 h down-regulated the expressions of the Cx43 by 13% in normal cardiac muscle cells（P〈0.01）.Hypertrophic cardiocytes can be induced by AGT Ⅱ in 48 h,and the down-regulation of the expression of total Cx43 protein in hypertrophic cardiocytes were more obvious than that in normal cardiac muscle cells under hypoxia condition（P〈0.01）.Valsartan can partly block the down-regulation of total Cx43 protein and the apoptosis of hypertrophic cardiocytes under hypoxia condition.Conclusion Hypoxia can down-regulate the expressions of the total Cx43 protein in cardiac muscle cells,especially in hypertrophic cardiocytes under hypoxia condition.Valsartan can partly block the changes and these maybe be relation to the effects of Valsartan on improving electrophysiology remodeling of hypertrophia myocardium induced by hypoxia.