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目的探讨银杏内酯B(ginkgolide B,GB)对心肌缺血再灌注损伤大鼠模型的心肌保护作用及其保护机制。方法建立大鼠心肌缺血再灌注模型,100只SD大鼠随机分为5组:假手术组,缺血再灌注模型组,GB高、中、低剂量组(60.0,30.0,15.0mg·kg-1),每组20只,于手术前灌胃给药7d。通过开胸结扎冠状动脉左前降支30min后松开再灌注,形成心脏局灶缺血再灌注模型。造模48h后检测心功能变化,染色计算梗死面积,病理切片染色评价氧化应激的程度,RT-PCR和Western blot分别监测心肌细胞中凋亡相关蛋白Bcl-2、Bax的变化,及p-Erk、p-Jnk、p-p38磷酸化水平变化。结果 GB预处理能显著改善大鼠缺血再灌注损伤后的心功能;GB中、高剂量组可显著降低Erk,Jnk及p38磷酸化;激活抗凋亡和抗氧化通路,发挥对心肌缺血再灌注的保护作用。结论在缺血再灌注前连续给药GB能缩小缺血再灌注损伤造成的梗死面积,改善心功能。这一保护作用可能是通过抗氧化和抗凋亡信号通路综合作用实现的。
Objective To investigate the myocardial protective effect of ginkgolide B (GB) on myocardial ischemia-reperfusion injury in rats and its protective mechanism. Methods The rat model of myocardial ischemia-reperfusion was established. 100 SD rats were randomly divided into 5 groups: sham operation group, ischemia-reperfusion model group, GB high, medium and low dose groups (60.0,30.0,15.0mg · kg -1), each group of 20, intragastric administration of 7d before surgery. Left anterior descending coronary artery was ligated by thoracotomy for 30 minutes, and reperfusion was released to establish a model of focal ischemia-reperfusion. The changes of cardiac function were detected 48 h after modeling. The area of infarction was calculated by staining. The extent of oxidative stress was evaluated by pathological staining. The changes of apoptosis-related proteins Bcl-2 and Bax in cardiomyocytes were detected by RT-PCR and Western blot respectively, Erk, p-Jnk, p-p38 phosphorylation level changes. Results GB preconditioning could significantly improve the cardiac function after ischemia / reperfusion injury in rats. GB and high dose groups could significantly reduce the phosphorylation of Erk, Jnk and p38, activate the anti-apoptotic and anti-oxidative pathways, Reperfusion protection. Conclusion Continuous administration of GB before ischemia-reperfusion can reduce infarct size caused by ischemia-reperfusion injury and improve cardiac function. This protective effect may be through antioxidant and anti-apoptotic signaling pathways to achieve.