瘦素预处理抑制细胞凋亡减轻大鼠心肌缺血/再灌注损伤的研究

Research of leptin pretreatment inhibits cellular apoptosis and reduces myocardial ischemia reperfusion injury in rats

目的:探讨瘦素(LEP)预处理抑制心肌细胞凋亡改善心肌缺血/再灌注损伤(MIRI)的作用途径.方法:将成年雄性SD大鼠24只,随机分为:正常组(Sham)、缺血/再灌注组(I/R)、瘦素+缺血/再灌注组(LEP+I/R)和LY(LY294002,LY)+LEP+I/R组.心电图检查验证大鼠MIRI模型成功后,2,3,5-三苯基氯化四氮唑(TTC)法检测心肌梗死面积,苏木精-伊红染色(HE)法和心肌酶检测心肌损伤程度,TENUL检测心肌组织凋亡程度,Western blot法检测Bcl-2、Bax和Cleaved Caspase-3等凋亡蛋白以及PI3K/Akt信号通路表达.结果:LEP预处理能够缩小I/R诱导的心肌梗死面积减轻心肌损伤,同时降低心肌细胞凋亡程度,该保护作用机制可能涉及PI3K/Akt信号通路的激活.LY作为PI3K信号通路的阻滞剂,能够逆转这种保护作用.结论:LEP预处理抑制心肌细胞凋亡可能与激活PI3K/Akt信号通路有关.

Objective:To explore how leptin(LEP)preconditioning inhibits myocardial cell apoptosis and improves myocardial ischemia/reperfusion injury(MIRI).Methods:Twenty-four adult male SD rats were randomly divided into normal group(Sham),ischemia reperfusion group(I/R),leptin+ischemia reperfusion group(LEP+I/R),and LY(LY294002,LY)+LEP+I/R group.ECG was employed to check whether the rat MIRI model was established successfully.The infarct size was detected by 2,3,5-triphenyltetrazolium chloride(TTC).The degree of myocardial damage was observed by hematoxylin-eosin staining(HE)and myocardial enzymes,and the degree of myocardial tissue apoptosis was measured by TUNEL.The expression of apoptotic proteins such as Bcl-2,Bax,and cleaved caspase-3,as well as the PI3K/Akt signaling pathway was assessed by Western blot analysis.Results:LEP pretreatment reduced the myocardial injury and the infarct size induced by I/R while reducing the degree of myocardial apoptosis.This protective effect might be effectuated via activation of the PI3K/Akt pathway.However,as a blocker of the PI3K pathway,LY could reverse this effect.Conclusion:The inhibition of cardiomyocyte apoptosis by LEP pretreatment may be related to the activation of PI3K/Akt signaling pathway.