摘要
目的:探讨藤黄酸(GA)对心肌缺血/再灌注损伤(MIRI)大鼠磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)信号通路及心肌损伤的影响.方法:将大鼠随机分为假手术组(Sham组)、模型组(Model组)、GA组和GA+PI3K抑制剂LY294002组(GLY组),Sham组仅穿线不结扎,其余组构建MIRI模型,观察心肌组织病理变化,并检测MIRI大鼠心肌细胞凋亡率、心肌损伤标志物[心肌肌钙蛋白I(cTnI)、乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)]和炎性因子[白细胞介素(IL)-1β、IL-18、IL-6、肿瘤坏死因子-α(TNF-α)]及心肌组织中Bax、Bcl-2、cleaved-capase 3、PI3K、磷酸化PI3K(p-PI3K)、AKT、磷酸化AKT(p-AKT)蛋白表达.结果:GA组心肌纤维疏松排列,少量炎性细胞浸润,心肌损伤减轻;与Model组比较,GA组大鼠细胞凋亡率、Bax、cleaved-capase 3、cTnI、LDH、CK-MB、IL-1β、IL-18、IL-6、TNF-α明显降低(P<0.05),Bcl-2、p-PI3K/PI3K、p-AKT/AKT蛋白表达明显升高(P<0.05);与GA组比较,GLY组大鼠细胞凋亡率、Bax、cleaved-capase 3、cTnI、LDH、CK-MB、IL-1β、IL-18、IL-6、TNF-α明显增加(P<0.05),Bcl-2、p-PI3K/PI3K、p-AKT/AKT蛋白表达明显降低(P<0.05).结论:GA通过激活PI3K/AKT信号通路抑制炎症反应,抑制心肌细胞凋亡,减轻大鼠MIRI,发挥心肌保护作用.
Abstract
Objective:To investigate the impacts of gambogic acid(GA) on the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT) signaling pathway and myocardial injury in myocardial ischemia-reperfusion injury (MIRI) rats.Methods:Rats were randomly grouped into sham surgery group(Sham group),model group(Model group),GA group,and GA+PI3K inhibitor LY294002 group(GLY group).The rats in Sham group only threaded without ligation,while the rats in other groups constructed MIRI models,the pathological changes of myocardial tissue were observed,and the apoptosis rate of myocardial cells,myocardial injury markers[cardiac troponin I(cTnI),lactate dehydrogenase(LDH),creatine kinase-MB(CK-MB)],inflammatory factors[interleukin(IL)-1β,IL-18,IL-6,tumor necrosis factor-α(TNF-α)],and the expression of Bax,Bcl-2,cleaved-capase 3,p-PI3K,PI3K,p-AKT,and AKT proteins in myocardial tissue of MIRI rats were detected.Results:The GA group showed loose arrangement of myocardial fibers,infiltration of a small amount of inflammatory cells,and mild myocardial injury.Compared with Model group,the apoptosis rate,Bax,cleaved-capase 3,cTnI,LDH,CK-MB,IL-1β,IL-18,IL-6,and TNF-αin GA group reduced obviously(P<0.05),the expression of Bcl-2,p-PI3K/PI3K,and p-AKT/AKT proteins increased obviously(P<0.05). Compared with GA group,the apoptosis rate,Bax,cleaved-capase 3,cTnI,LDH,CK-MB,IL-1β,IL-18,IL-6,and TNF-αin GLY group increased obviously(P<0.05),the expression of Bcl-2,p-PI3K/PI3K,and p-AKT/AKT proteins reduced obviously(P<0.05).Conclusion:GA inhibits inflammatory response,inhibits cardiomyocyte apoptosis,reduces MIRI in rats,and exerts myocardial protective effects by activating the PI3K/AKT signaling pathway.
维普
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