肾脏缺血后处理对兔急性缺血再灌注心肌细胞凋亡和Bcl-2、Bax蛋白表达的影响

目的研究肾脏缺血后处理对兔急性缺血再灌注心肌细胞凋亡的影响,并探讨其保护机制。方法24只新西兰大白兔随机分为3组,每组8只。（1）缺血再灌注组（IR组）：结扎左冠状动脉前降支1h,再灌注6h。（2）肾脏缺血后处理组（RI-Post组）：操作同IR组,在再灌注即刻用动脉血管夹反复夹闭左侧肾动脉（阻断30S,再通30S,重复3次）,再灌注6h。（3）药物干预组（MI组）：结扎左冠状动脉前降支1h,再灌注前10min给予蛋白激酶C抑制剂-GF109203X（O．05mg／kg）耳缘静脉注射持续10min,再灌注即刻行RI-Post组操作,最后心肌再灌注直至6h。实验结束,采用Tunel法检测24只兔梗死区的心肌细胞凋亡,用免疫组化法检测Bax和Bcl-2蛋白在心肌细胞中的表达水平。结果肾脏缺血后处理组与对照组和药物干预组比较,心肌细胞凋亡指数明显减少（P〈0．05）,Bcl-2表达明显增多（P〈0．01）,Bax表达明显减少（P〈0．05）;而药物干预组与对照组相比各检测指标无明显差别（P〉0．05）。结论肾脏缺血后处理可减少急性缺血再灌注后心肌细胞凋亡,并影响Bcl-2、Bax蛋白的表达,从而对缺血心肌产生保护作用,其保护机制可能与激活蛋白激酶C有关。

Remote postconditioning by brief renal ischemia and reperfusion reduces acute myocardial ischemia and reperfusion induced myocardial apoptosis in rabbits

OBJECTIVES: To observe the effects of renal ischemic postconditioning (RI-Post) on myocardial apoptosis in rabbits with acute myocardial ischemia and reperfusion. METHODS: All rabbits were subjected to 60 minutes ischemia by left anterior descending coronary artery occlusion (LADO) and 6 hours reperfusion. The rabbits are randomly divided into 3 groups (n = 8 in each group): (1) Ischemia-reperfusion (IR): LADO and reperfusion without additional intervention; (2) RI-Post: after 60 minutes of LADO, the left renal artery was occluded for 30 seconds and reperfused for 30 seconds and repeated 3 times, then the coronary artery was reperfused for 6 hours; (3) Medication intervention (MI): 10 minutes before coronary reperfusion, rabbits were treated with PKC antagonist GF109203X (0.05 mg/kg, IV), followed by RI-Post treatment and 6 hours coronary reperfusion. Myocardial apoptosis was measured by TUNEL and the myocardial Bcl-2 and Bax protein expressions were assessed by immunohistochemistry. RESULTS: Compared with the IR group and the MI group, myocardial apoptosis was significantly reduced (P < 0.05) and the Bcl-2 protein expression increased (P < 0.01) while the Bax protein expression decreased (P < 0.05) in the RI-Post group. CONCLUSIONS: Remote renal postconditioning applied right before the onset of coronary artery reperfusion can reduce the myocardial apoptosis induced by myocardial ischemia and reperfusion and up-regulate Bcl-2 while down-regulate Bax expression possibly by activation of protein kinase C.