AngⅡ诱导大鼠心肌细胞肥大过程中分泌型卷曲相关蛋白5表达上调

Ang Ⅱ induces up-expression of secreted frizzled-related protein 5 in cardiomyocyte hypertrophy of rats

目的探讨分泌型卷曲相关蛋白5(s FRP5)在大鼠心肌细胞肥大中表达的机制。方法体外培养乳鼠心肌细胞,用血管紧张素Ⅱ(AngⅡ10-6mmol/L,48 h)诱导心肌细胞肥大。应用替米沙坦和Y27632分别阻断血管紧张素1型受体(AT1R)及Rho/Rho激酶(Rho/ROCK)信号通路;PD98059、SB203580及SP600125分别阻断p38 MAPK、ERK1/2及JNK通路;RT-PCR检测s FRP5的表达;Western blot检测s FRP5、ROCK1、ROCK2、总MYPT1、p-MYPT1表达。结果 AngⅡ诱导的心肌细胞肥大致s FRP5表达上调(P<0.05),Y27632下调s FRP5的表达(P<0.05);替米沙坦下调ROCK1的表达(P<0.05);SP600125明显降低s FRP5表达的增加(P<0.05)。结论在AngⅡ诱导的心肌细胞肥大过程中,主要通过Rho/ROCK1/JNK通路上调s FRP5的表达。

Objective To investigate the mechanism of secreted frizzled-related P rotein 5（ s FRP 5） expression in cardiomyocyte hypertrophy. Methods In vivo experiment,neonatal rat ventricular myocytes were exposed to Ang Ⅱ（ 10-6 mmol/L,48 h）. Telmisartan,Y27632,P D98059,SB203580 and SP 600125 were used to block angiotensin type 1 receptor（ AT1 R）,Rho/ROCK,p38 MAP K,ERK1/2 and JNK pathway,respectively. Western blot was applied to determine the expressions of s FRP 5, ROCK1, ROCK2, total MYP T1,p-MYP T1. RT-P CR was used to determine s FRP 5 expression. Results There was significant inhibition of s FRP 5 expression when treated with Y37632 and SP 699125,but less with SB203580 and P D98059 in AngⅡ-induced cardiomyocytes. Moreover,telmisartan down-regulated the expression of ROCK1,but no effect on the expression of ROCK2. Conclusions The expression of s FRP 5 is up-regulated mainly by Rho/ROCK1/JNK pathway in cardiomyocyte hypertrophy induced by Ang Ⅱ.