心肌缺血再灌注损伤模型大鼠经艾塞那肽预处理后心肌细胞的凋亡

Cardiomyocyte apoptosis in rats with myocardial ischemia/reperfusion injury after Exendin-4 pretreatment

背景:有研究表明艾塞那肽可改善心肌梗死和心力衰竭等过程发挥心血管保护作用,但其对缺血再灌注损伤后心肌细胞凋亡的作用尚未阐明。目的:艾塞那肽预处理心肌缺血再灌注损伤模型大鼠,观察其对心肌组织细胞凋亡及对凋亡因子Bcl-2、Bax表达的影响。方法:建立心肌缺血再灌注损伤模型大鼠,用艾塞那肽进行预处理,并设缺血再灌注组和假手术组作对照。结果与结论:免疫组织化学染色、原位末端标记检测RT-PCR检测显示,与缺血再灌注组比较,艾塞那肽组Bcl-2的mR NA和蛋白表达显著升高(P<0.05),Bax mR NA和蛋白表达显著降低(P<0.05),心肌细胞凋亡指数显著降低(P<0.05)。结果证实,艾塞那肽对大鼠心肌缺血再灌注有保护作用,其机制可能是通过上调Bcl-2的表达,下调Bax的表达,从而抑制心肌细胞凋亡有关。

BACKGROUND： Exendin can regulate blood glucose, blood lipid and blood pressure, exert anti-inflammation and anti-oxidative stress effects, improve myocardial infarction and heart failure, and protect heart vessels. However, the effect on the apoptosis of cardiac muscle cells after ischemia/reperfusion injury remains unclear. OBJECTIVE： To observe the effects of Exendin-4 pretreatment on the cardiomyocyte apoptosis and the expression of Bcl-2 and Bax in rats with myocardial ischemia/reperfusion injury. METHODS： The myocardial ischemia/reperfusion injury model was established in rats and then received Exendin-4 pretreatment. Ischemia/reperfusion group and sham operation group were set. RESULTS AND CONCLUSION： Immunohistochemical staining, TUNEL and reverse transcriptase-polymerase chain reaction results showed that Bcl-2 protein and m RNA expression levels in the Exendin-4 group were significantly increased（P〈0.05）, while Bax protein and m RNA expression levels were significantly decreased compared with ischemia/reperfusion group（P〈0.05）. In addition, apoptosis index was more significantly decreased in the Exendin-4 group than in the ischemia/reperfusion group（P〈0.05）. Exendin-4 can protect rat heart muscle against ischemia/reperfusion injury and effectively inhibit the apoptosis of cardiomyocytes, and the underlying mechanism is mediated by up-regulating Bcl-2 expression and down-regulating Bax expression.