心衰大鼠心肌SRCa^(2+)释放通道数量及其mRNA表达的变化及培哚普利干预的影响

Effects of Perindopril on amount and mRNA expression of Ca^(2+) release channels of myocardial sarcoplasmic reticulum in rats with chronic heart failure

目的 探讨慢性心衰心肌肌浆网 (SR)Ca2 + 释放通道 (RyR2 )数量及其mRNA表达的变化及ACEI干预的影响及意义。方法 通过结扎大鼠左冠脉建立慢性心衰模型 ,以培哚普利进行干预 ,对照观察血流动力学、[3 H]-ryanodine与左室心肌RyR2 最大结合量 (Bmax)和Kd 值、RyR2 mRNA表达水平。结果 与对照组 (C组 )相比 ,心衰组 (F组 )LVEDP显著升高 (P <0 .0 1) ,+dp/dtmax、-dp/dtmax显著降低 (P <0 .0 1) ,培哚普利组 (P组 )LVEDP显著低于F组 (P <0 .0 1) ,+dp/dtmax、-dp/dtmax显著高于F组 (P<0 .0 1)。F组 [3 H]-ryanodine与RyR2 最大结合量Bmax显著低于C组 (P <0 .0 1) ,P组显著高于F组 (P <0 .0 1) ,三组Kd 值无显著差异 (P >0 .0 5 ) ;F组RyR2 mRNA表达水平显著低于C组 (P <0 .0 1) ,P组显著高于F组 (P <0 .0 1)。结论 慢性心衰心肌SRCa2 + 释放通道数量及其mRNA表达水平降低 ,培哚普利长期干预慢性心衰 ,能够增加RyR2 基因表达 ,增加RyR2 数量 。

Objective To study the effects of ACE1 on amount and mRNA expression of Ca 2+ release channels(RyR 2) of myocardial sarcoplasmic reticulum(SR) in prevention and treatment of chronic heart failure.Methods After the model of chronic heart failure was established with ligation of left corongary artery in rats,the animals were prevented and treated with Perindopril. Hemodynamic parameters, B max and K d of [ 3H]-ryanodine binding to RyR 2、RyR 2 mRNA content were determined.Results Compared with the control group(group C),LVEDP in the heart faliure group (group F)increased(P<0.01),while+dp/dt max and -dp/dt max decreased significantly(P<0.01).LVEDP was lower but +dp/dt max and -dp/dt max significantly higher in the Perindopril treated group(group P)than those in group F(P<0.01).B max of [ 3H]-ryanodine binding to RyR 2 and mRNA content of RyR 2 in group F were lower than those in group C(P<0.01),and these in group P were higher than those in group F(P<0.01). There were no significant difference of K d among the three groups(P>0.05).Conclusion The amount and mRNA expression of RyR 2 of myocardial sarcoplasmic reticulum(SR) decreased in chronic heart failure.Perindopril can improve mRNA expression and amount of RyR 2 of myocardial SR in prevention and treatment of chronic heart failure, thus contributing to the improvement of myocardial function.