缬沙坦抑制血管紧张素Ⅱ刺激下心肌细胞缝隙连接蛋白43表达的上调

摘要

目的 研究血管紧张素Ⅱ(AngⅡ)刺激心肌细胞肥大后,缝隙连接蛋白43(Cx43)表达的变化及缬沙坦的干预作用.方法 分离培养大鼠心肌细胞,分为对照组,AngⅡ组(AngⅡ1.0×10 6 mol/L)和缬沙坦组(AngⅡ1.0×10 6 mol/L+缬沙坦1.0×10 6 mol/L).另外将缬沙坦以1.0×10(5)、1.0×10 6和1.0×10 7 mol/L刺激分为A组、B组和C组.先用AngⅡ诱导心肌肥大24 h后,采用免疫荧光法和免疫印迹蛋白法观察心肌细胞Cx43蛋白表达以及缬沙坦的干预作用.结果 与对照组比较,AngⅡ组心肌细胞明显肥大,蛋白质含量明显增加,Cx43蛋白表达明显上调；与Ang Ⅱ组比较,缬沙坦组拮抗AngⅡ刺激下Cx43蛋白的上调,并呈明显浓度依赖性下降.与A组比较,B、C组Cx43蛋白表达下降(P＜0.05).结论 AngⅡ刺激心肌细胞24 h后,通过AngⅡ1型受体信号通路.导致Cx43蛋白表达浓度依赖性上调,缬沙坦明显抑制其上调,Cx43上调可能与心肌肥大过程有关.%Objective To study the intervention effect of valsartan on expression of connexin 43 (Cx43) protein in angiotensin Ⅱ (AngⅡ )-stimulated cardiomyocytes. Methods Cultured rat car-diomyocytes were randomly divided into control group, 1. 0X 10~6 mol/L AngⅡ group.and 1. OX l0-6 mol/L valsartan group which was further divided into 1. 0X 10 6 mol/L valsartan group (group A),l. 0X 10~6 mol/L valsartan group(group BO,and 1. 0X 10 7mol/L valsartan group (group C). Intervention effect of valsartan on Cx43 protein expression in cardiomyocytes after 24 h exposure to Ang fl was detected by flow cytometry and immunofluorescence, respectively. Results The expression level of Cx43 protein in cardiomyocytes was significantly higher in Ang Ⅱ group than in control group and valsartan group. Conclusion Ang Ⅱ up-regulates and valsartan down-regulates the expression of Cx43 protein in a dose-dependent manner through the type T Ang Ⅱ receptor signal pathway. Up-regulated expression of Cx43 protein may be related with hypertrophy of cardiomyocytes.