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目的对比观察维拉帕米后处理和缺血后处理(IPC)对大鼠心肌缺血再灌注损伤(MIRI)的保护作用。方法60只雄性Wistar大鼠,将其随机分为假手术(Sham)组、模型(MIRI)组、维拉帕米后处理(VP)组和IPC组,每组10只。除Sham组仅穿线不结扎外,其余大鼠缺血30 min,再灌注120 min制备MIRI模型,VP组于再灌注前60 min灌胃给予维拉帕米5 mg/kg,IPC组于缺血30 min后再灌注30 s、再结扎30 s,重复3个循环后再灌注120 min。实验结束后计算心肌梗死面积(MIS),HE染色观察组织形态学变化,检测血清Ca~(2+)、丙二醛(MDA)、一氧化氮(NO)、内皮素(ET)-1含量及心肌酶[天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH),肌酸激酶(CK)]、超氧化物歧化酶(SOD)活性。结果与Sham组比较,MIRI组大鼠MIS明显扩大,血清AST、CK及LDH活性明显升高,SOD活性明显降低,Ca~(2+)、MDA及ET-1含量明显升高,NO含量明显降低,差异均有统计学意义(P<0.05,P<0.01);心肌组织出现严重的病理损伤。与MIRI组比较,VP和IPC组大鼠MIS明显缩小,血清AST、CK及LDH活性明显降低,SOD活性明显升高,Ca~(2+)、MDA及ET-1含量明显降低,NO含量明显升高,差异均有统计学意义(P<0.05,P<0.01);VP和IPC组心肌组织未见严重的病理损伤;且二者上述各指标水平相当(P均>0.05)。结论维拉帕米后处理与IPC对大鼠MIRI均具有保护作用,其机制与抗过氧化损伤、钙超载,改善内皮功能,减轻心肌病理损伤有关。
Objective To compare the protective effects of verapamil postconditioning and postconditioning (IPC) on myocardial ischemia-reperfusion injury (MIRI) in rats. Methods Sixty male Wistar rats were randomly divided into sham group, model group (MIRI), verapamil (VP) group and IPC group, with 10 rats in each group. MIRI model was established after ischemia for 30 min in Sham group and reperfusion for 120 min in Sham group. Verapamil 5 mg / kg was given intragastrically in VP group 60 min before reperfusion, After 30 min, reperfusion 30 s, then ligation 30 s, repeated 3 cycles after reperfusion 120 min. After the experiment, the area of myocardial infarction (MIS) was calculated and the histological changes were observed by HE staining. The content of Ca2 +, malondialdehyde (MDA), nitric oxide (NO) and endothelin (ET) (AST, LDH, CK) and SOD activity were measured. Results Compared with Sham group, MIS in MIRI group was significantly increased, serum AST, CK and LDH activity were significantly increased, SOD activity was significantly decreased, Ca ~ (2 +), MDA and ET-1 levels were significantly increased, NO content was significantly Decreased, the differences were statistically significant (P <0.05, P <0.01); myocardial tissue serious pathological injury. Compared with the MIRI group, the rats in the VP and IPC groups were significantly reduced MIS, serum AST, CK and LDH activity was significantly decreased, SOD activity was significantly increased, Ca ~ (2 +), MDA and ET-1 levels were significantly reduced, NO content was significantly (P <0.05, P <0.01). No significant pathological damage was found in the myocardium of VP and IPC groups, and the above indexes were comparable (P> 0.05). Conclusion Verapamil postconditioning and IPC have a protective effect on MIRI in rats. The mechanism is related to anti-oxidative damage, calcium overload, endothelial function improvement and myocardial pathological damage.