血管紧张素-(1-7)在拮抗血管紧张素Ⅱ诱导心肌细胞Cx43间隙连接上调中的作用  

Angiotensin-(1-7) antagonizes angiotensinⅡ induced cardiac myocyte Cx43 gap junction up-regulation

作　　者：王业松[1] 马虹[1] 胡苑[1] 曾武涛[1] 张惠忠[2] 陈健文[3] 

机构地区：[1]中山大学附属第一医院心内科,广东广州510080 [2]中山大学附属肿瘤医院病理科,广东广州510060 [3]中山大学生理实验科,广东广州510080

出　　处：《中国心血管杂志》2005年第5期322-326,共5页Chinese Journal of Cardiovascular Medicine

基　　金：广州市科委基金资助(编号:200J1-CO181)

摘　　要：目的探讨血管紧张素-(1-7)[Ang-(1-7)]在血管紧张素Ⅱ(AngⅡ)诱导心肌细胞Cx43间隙连接中作用.方法 AngⅡ处理培养心肌细胞24h.PD98059和Ang-(1-7)在AngⅡ刺激细胞前1h加到培养基中,对照组加等体积药物溶剂DMSO.用Western blot分析和电镜观察心肌细胞Cx43表达和间隙连接.结果 Western blot分析显示用10-9～10-6mol/LAngⅡ刺激细胞24h,Cx43的表达与对照组相比呈浓度依赖性增加;用AngⅡ0.1μmol/L刺激心肌细胞24h,与对照组相比Cx43表达上调、磷酸化ERK1/2活性增加(P＜0.01),ERK1/2激酶特异性抑制剂1μmol/LPD98059和0.1μmol/LAng-(1-7)能阻断AngⅡ上调Cx43表达和磷酸化ERK1/2活性增加.电镜观察证明用AngⅡ0.1μmol/L刺激心肌细胞24h,AngⅡ处理组细胞间隙连接数目和大小较对照组增加(P＜0.05),0.1μmol/LAng-(1-7)能阻断AngⅡ增加心肌细胞间隙连接数目和大小.结论 Ang-(1-7)通过抑制磷酸化ERK1/2活性增加,从而拮抗AngⅡ上调培养新生鼠心肌细胞Cx43间隙连接.Objective To investigate the role of angiotensinl-7 [ Ang-（ 1-7）] in angiotensin Ⅱ （Ang Ⅱ ） induced Cx43 gap junction in cultured neonatal rat cardiac myocytes. Methods The Cardiac myocyte cultures were treated with Ang Ⅱ for 24h, which were pretreated with PD98059 or Ang-（ 1-7） for 60 rain before AngⅡ treatment. The controls were treated with equal amount of DMSO. Cardiac myocytes Cx43 expression and gap junction were characterized by Westem blot and electron microscope. Results Westem blot analysis revealed Cx43 content concentration-dependent increase in cells treated with 10^-9-10^-6 mol/L Ang Ⅱ for 24h ; Cx43 expression and phosphorylated extracellelar signal regulated kinase（ PERK） 1/2 activity increase in ceils treated with 0.1μmol/L Ang Ⅱ for 24h （ P 〈 0.01 compared with control）, which was inhibited by the presence of 1μmol/L PD98059, a specific inhibitor of ERK1/2 kinase and 0. 1μmol/L Ang-（ 1-7） . Electron microsocopy demonstrated increases in the number and size of gap junction profiles in cells exposed to 0. μmol/L Ang Ⅱ for 24h（ P〈 0.05 compared with control）. This response was inhibited by the presence of 0. μmol/L Ang-（ 1-7）. Conclusion： Ang-（ 1-7） antagonizes the effects of AngⅡ on up-regulating Cx43 gap junction in cultured neonatal rat cardiac myocytes via inhibiting P-ERK1/2 activity increase.

关 键 词：血管紧张素 心肌细胞 连接蛋白 间隙连接 细胞外信号调节激酶 

分 类 号：R541[医药卫生—心血管疾病]