药理预适应对兔急性心肌缺血保护作用的研究

目的:观察金纳多和硝酸甘油注射液药理预适应对在体兔心肌缺血/再灌注后热休克蛋白70(HSP70)表达的诱导作用并探讨其心肌保护作用机制。方法新西兰大白兔20只,随机分为4组,每组5只。假手术组开胸后只穿线不结扎,生理盐水组、金纳多组和硝酸甘油组建立心肌缺血/再灌注模型,并于缺血前0.5h分别给予生理盐水、金纳多注射液和硝酸甘油注射液预处理。采用蛋白质免疫印迹法(Western blot)检测各组缺血区和非缺血区心肌组织HSP70含量,并检测血清一氧化氮(NO)、丙二醛(MDA)含量及总超氧化物歧化酶(T SOD)、肌酸激酶(CK)活性变化。结果假手术组HSP70很少表达;其余3组HSP70含量均有明显表达,其中,生理盐水组缺血区和非缺血区HSP70表达分别达假手术组的2.5和2.1倍,金纳多组达17.6和20.7倍,硝酸甘油组达28.1和29.1倍。生理盐水组血清T SOD水平明显降低,MDA和CK水平明显升高(P均<0.01)。金纳多和硝酸甘油组T SOD水平轻度下降,与假手术组和生理盐水组比较差异均有显著性;MDA和CK水平均明显低于生理盐水组,NO明显高于生理盐水组(P<0.05或P<0.01)。硝酸甘油组T SOD、CK活性和NO含量均明显高于金纳多组(P均<0.01),两组MDA水平差异无显著性。结论金纳多和硝酸甘油注射液可诱导心肌缺血/再灌注后HSP70过量表达,从而对心肌起保护作用;金纳多和硝酸甘油的抗氧化作用和细胞保护作用可能与HSP70有关。

Study on protective effects of pharmacological preconditioning on rabbits with myocardial ischemia/reperfusion

Objective: To observe the effects of ginaton and nitroglycerin injection on expression of heat shock protein 70 (HSP70) and cardioprotective mechanism in rabbits with ischemia/reperfusion (I/R). Methods : Twenty New Zealand white rabbits were randomly divided into four groups, 5 rabbits being in each group. The model was not replicated in the sham-operated group. Myocardial I/R models were replicated in animals in normal saline, ginatone and nitroglycerin injection groups and were administered with normal saline, ginatone and nitroglycerin injection respectively 0.5 hour before ischemia. Western blot was used to measure HSP70 of ischemia and non-ischemia myocardium and the expression of HSP70 was analyzed semiquantitatively . Serum nitric oxide (NO), malondialdehyde (MDA) contents and total superoxide dismutase (TCD*2SOD) , creatine kinase (CK) activity were measured. Results: HSP70 was less expressed in sham-operated group and more expressed in normal saline group, ginaton group and nitroglycerin injection group. Expression of HSP70 of ischemia and non-ischemia myocardium in normal saline group was 2.5CD*2 and 2.1CD*2fold, in ginaton group 17.6CD*2 and 20.7CD*2fold and in nitroglycerin group 28.1CD*2 and 29.1CD*2fold to that in the shamCD*2operated group, respectively. The activity of TCD*2SOD was lower while MDA and CK levels were higher in the normal saline group than those in the sham-operated group (all P<0.01). In ginaton group and nitroglycerin group, TCD*2SOD slightly decreased compared with sham-operated group and normal saline group, MDA and CK levels decreased and NO levels increased significantly compared with those of normal saline group (P<0.05 or P<0.01). TCD*2SOD, CK and NO levels were higher in nitroglycerin group than those of the ginaton group (all P<0.01), but no significant difference in MDA level was found between the two groups. Conclusion: Ginaton and nitroglycerin injection can induce expression of HSP70 excessively after I/R ; their cardioprotective mechanism may be related to HSP70.