前列地尔预适应对兔急性心肌缺血再灌注的早期保护作用及机制的实验研究

The Early Protective Effects and Mechanism of Prostaglandin E1 Pretreatment on Myocardial Injury Induced by Ischemia Reperfusion in Rabbits Hearts

目的:通过建立日本大耳白兔急性心肌缺血再灌注模型,观察前列地尔对兔心肌缺血再灌注的早期保护作用,并初步探讨前列地尔药物预适应保护心肌的机制。方法:将40只日本大耳白兔随机分为缺血再灌注组(IR)、缺血预适应组(IP)、前列地尔预适应组(PGE1)及前列地尔+KATP通道阻断剂格列本脲(GLI)组,分别测定各组血清肌酸激酶同工酶(CK-MB),肌钙蛋白I(cTnI),超氧化物歧化酶(SOD),丙二醛(MDA)含量;染色称重,测定心肌梗死范围;光镜下观察心肌组织学形态。结果:1、就四个实验组的肌酸激酶同工酶(CK-MB)、肌钙蛋白I(TnI)测量值而言,IP组和PGE1组与IR组比较,IP组和PGE1组比IR组低,具有统计学意义(P<0.05);GLI组与IR组比较,无统计学意义(P>0.05)。2、四个实验组的超氧化物歧化酶(SOD)测量值,IP组和PGE1组与IR组比较,IP组和PGE1组比IR组高,具有统计学意义(P<0.05):GLI组与IR组比较,无统计学意义(P>0.05):丙二醛(MDA)测量值IP组和PGE1组与IR组比较,IP组和PGE1组比IR组低,具有统计学意义(P<0.05);GLI组与IR组比较,无统计学意义(P>0.05);3、四个实验组的心肌梗死面积比较,各组的全心重与心室重比较,无统计学意义(P>0.05);IP组和PGE1组与IR组比较,IP组和PGE1组比IR组小,具有统计学意义(P<0.05);GLI组与IR组比较,无统计学意义(P>0.05)。结论:前列地尔预适应减少血清CK-MB、cTnI的漏出及心肌梗死的范围,并且提高心肌抗氧化能力,可以模拟缺血预适应,对急性心肌缺血再灌注损伤具有有效的保护作用,并且是通过KATP通道开放激活而发挥预适应样的保护作用的。因此将前列地尔预适应与冠状动脉旁路术、心肺旁路术、心脏瓣膜置换术及经皮穿刺冠状动脉腔内成形术等结合起来,广泛地应用于临床,具有乐观的前景。

Objective： To observe the early protective effect of prostaglandin E1（PGE1） on myocardial ischemia reperfusion through the establishment of rabbit model and investigate the preliminary mechanism.Methods： Forty Japanese white rabbits were divided into four groups： ischemia-reperfusion group（IR）,ischemic preconditioning group（IP）,alprostadil preconditioning group（PGE1） and alprostadil combined with Glibenclamide（GLI） group.The creatine kinase isoenzyme（CK-MB）,troponin I（cTnI）,superoxide dismutase（SOD） and malondialdehyde（MDA） in rabbit serum of each group were measured.The size of myocardial infarction was measured by pathological examination.Myocardial histological morphology was observed by microscope.Results： The CK-MB,cTnI and MDA were significantly decreased and the SOD was significantly increased in IP group and PGE1 group compared with those in IR group（P0.05）.But there was no significant difference between GLI group and IR group（P0.05）.The size of myocardial infarction was significantly large in IP group and PGE1 group compared with that in IR group（P0.05）.No significant difference was observed between GLI group and IR group（P0.05）.Conclusion： The range of myocardial infarction and serum CK-MB,cTnI leakage reduced after alprostadil preconditioning,which improved cardiac antioxidant capacity,simulated the ischemic preconditioning,and effectively protected the acute myocardial ischemia reperfusion injury,meanwhile,preconditioning protection role should be actived by KATPchannel openning up.Therefore,alprostadil preconditioning combinated with coronary artery bypass,cardiopulmonary bypass,cardiac valve replacement and percutaneous transluminal coronary angioplasty have an optimistic outlook in the future and widely used in clinical practice.