乙醛脱氢酶2在法舒地尔心肌保护作用中的机制  

Mechanism exploration of aldehyde dehydrogenase 2 in the cardioprotection of fasudil

作　　者：叶红伟 康品方[2] 王洪巨[2] 李正红[3] 关宿东[3] 高琴 

机构地区：[1]安徽省组织移植重点实验室 [2]蚌埠医学院第一附属医院心血管内科 [3]蚌埠医学院生理学教研室,安徽蚌埠233030

出　　处：《中国老年学杂志》2013年第5期1070-1072,共3页Chinese Journal of Gerontology

基　　金：国家自然科学基金资助项目(No.81000074);安徽省自然科学基金资助项目(No.090413097)

摘　　要：目的探讨乙醛脱氢酶2(ALDH2)是否参与Rho激酶抑制剂法舒地尔的心肌保护作用,并分析其可能机制。方法采用离体大鼠心脏,结扎冠状动脉左前降支30 min模拟局部心肌缺血,松开结扎线恢复灌流120 min复制心肌缺血/再灌注(I/R)模型。实验分4组:I/R组、法舒地尔组、ALDH2抑制剂氨基氰(CYA)组和法舒地尔+CYA(联合组)组。连续记录左心室动力学变化,再灌注期间收集冠脉流出液测定乳酸脱氢酶(LDH)含量;RT-PCR检测ALDH2 mRNA表达以及Bcl-2/Bax比值的变化。结果与I/R组比,法舒地尔组明显促进了左室发展压、左心室内压最大上升和下降速率、左心室做功的恢复,降低复灌期冠脉流出液中LDH的释放,ALDH2 mRNA表达增加,Bcl-2/Bax比值增高。ALDH2抑制剂CYA明显减弱法舒地尔的作用,抑制了心室动力学指标的恢复,LDH释放增多,ALDH2 mRNA表达降低,Bcl-2/Bax比值降低。结论法舒地尔抑制Rho激酶信号通路发挥心肌保护作用,其机制可能与激动ALDH2、抑制凋亡发生有关。Objective To investigate whether aldehyde dehydrogenase 2 （ALDH2） was involved in the cardioprotection of fasudil, the inhibitor of Rho-kinase, and explore the mechanism. Methods Hearts isolated from male SD rats were subjected to 30 minutes of re- gional ischemia （occlusion of left anterior descending artery） followed by 120 minutes of reperfusion. The experiment was divided into 4 groups： I/R, Fasudil, ALDH2 inhibitor CYA and Fasudil ＋ CYA groups. The left ventricular hemodynamics were continuous recorded, the coronary effluent was collected during the reperfusion period to determinate lactate dehydrogenase （LDH） levels. ALDH2 mRNA expression and the ratio of Bcl-2/Bax were detected by RT-PCR. Results Compared with I/R group, fasudil significantly increased the restore of left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure and rate pressure product, reduced LDH release during reperfusion period, ALDH2 mRNA expression and the ratio of Bcl-2/Bax were increased. CYA, the ALDH2 inhibitor reduced the role of fa- sudil, which inhibited the recovery of ventricular hemodynamical parameters, increased LDH release, it also inhibited the expression of AL- DH2 mRNA, and Bcl-2/Bax ratio was decreased. Conclusions Fasudil can play myocardial protection by inhibiting Rho-kinase signaling pathway, and maybe related with excitement of ALDH2 and inhibiting apoptosis happening.

关 键 词：心脏 缺血 再灌注损伤 乙醛脱氢酶2 RHO激酶 法舒地尔 氨基氰 

分 类 号：R363.2[医药卫生—病理学]