缺血预适应减轻心肌缺血-再灌注损伤的机制研究

目的:探讨缺血预适应在预防或减轻心肌细胞损伤和心肌细胞凋亡中的作用。方法:采用新西兰兔制备缺血预适应(IP)、缺血-再灌注损伤(RI)、持续缺血(CI)和正常对照组(control)4种模型。模型制备后采集血标本,以及心脏病变部位心肌标本,并常规组织学处理、石蜡包埋后切片。结果:①CI组心肌梗死面积最大,其次为RI组,均明显高于IP组(P<0.01);②RI组和CI组的血清各项心肌酶含量均明显高于control组和IP组(P<0.01),而后两组之间则无显著性差异(P>0.05);③RI组和CI组的血浆SOD活性均明显降低,尤其以RI组最为显著,与IP组和control组相比较(P<0.01);而在control组和IP组之间则无显著性差异(P>0.05);RI组的血清丙二醛含量明显高于其他各组(P<0.01);④缺血预适应组虽然也有一定的心肌细胞凋亡率,但较再灌注损伤组和持续缺血组则明显为低(P<0.001)。⑤从各组心肌梗死面积与细胞凋亡发生率的相关分析中,可见心肌凋亡细胞的数量与心肌梗死面积的大小之间有明显的正相关(RI、IP和CI组的γ值分别为0.92,0.94和0.87,P<0.01)。结论:在心肌缺血缺氧早期,心肌梗死面积的大小与心肌细胞凋亡数量的多少有关;缺血预适应处理能减轻缺血-再灌注和持续缺血引起的心肌损伤,减少心肌梗死面积;同时能明显减少这2种情况所诱导的心肌细胞凋亡的发生率。

Effect of ischemic preconditioning on reducing myocardial cell injuries

Objective: To study the role of ischemic preconditioning in reducing myocardial cell injuries and reducing myocyte apoptosis. Methods: The models of ischemic preconditioning (IP), ischemia-reperfusion injury (RI), continuous ischemia (CI) and control were made with rabbits. Results: The serum contents of AST,LDH,CK and HBD in RI and CI groups were higher than those in IP and control groups (P<0.01), which meaned that there was severe damage in myocytes of RI and CI groups. Plasma activities of SOD in RI and CI groups decreased (P<0.01,compared with IP and control groups), but there was no statistic significance between IP and control groups. The contents of serum MDA in RI group was also higher than other groups (P<0.01). The rate of apoptotic myocytes in IP group (24.44±2.96)% was higher than that in control (0.71±0.51)%, but was lower than that in CI (29.56±3.08)% and RI groups (43.33±4.92)% significantly (P<0.001). DNA ladders were showed in RI group (4/10), CI(2/10) and IP(1/10). Also, the number of myocyte apoptosis in each group was positively correlated with the size of myocardial infarction.(γ=0.92,0.94 vs 0.87, respectively in RI, IP and CI groups,P<0.01). Conclusion: IP could prevent myocardial cells injury induced by ischemia-reperfusion and continuous ischemia- reduce the size of myocardial cell infarction, and also the rates of myocyte apoptosis in those situations at the same time, which means ischemia preconditioning can prevent ischemia-reperfusion injury partly by reducing the myocyte apoptotic rate. The size of myocardial infarction was significantly correlated with the number of myocyte apoptosis.