紫檀芪通过调控细胞自噬对抗大鼠心肌缺血/再灌注损伤

目的:观察紫檀芪对大鼠心肌缺血/再灌注损伤(MI/RI)的影响,探讨其保护机制是否与调控心肌自噬有关。方法:72只SD大鼠随机分为六组(n=12),分别为假手术组、MI/RI组、阿司匹林组、紫檀芪低剂量组、紫檀芪中剂量组和紫檀芪高剂量组,干预14 d后,构建MI/RI模型,观察心肌组织病理改变、测定心肌梗死面积及心肌组织中细胞自噬信号相关蛋白Atg5、Beclin1、LC3Ⅰ/Ⅱ和p62蛋白表达水平,测定血清心肌损伤指标乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB),氧化应激指标丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GSH-Px)的含量。结果:心肌组织病理学检查提示,与假手术组比较,MI/RI组心肌纤维明显断裂,部分坏死,部分细胞结构模糊; 与MI/RI组比较,各治疗组心肌纤维断裂明显减少,细胞结构较清晰(P<0.05)。与假手术组比较,MI/RI组心肌梗死面积、LDH、CK-MB及MDA显著升高(P<0.05),SOD、CAT及GSH-Px显著降低(P<0.05),Atg5、Beclin1及LC3 Ⅰ/Ⅱ蛋白明显升高(P<0.05),p62蛋白显著降低(P<0.05); 与模型组比较,各治疗组心肌梗死面积、LDH、CK-MB和MDA显著降低(P<0.05),SOD、CAT、GSH-Px明显升高(P<0.05),Atg5、Beclin1及LC3 Ⅰ/Ⅱ 蛋白表达降低(P<0.05),p62蛋白表达升高(P<0.05)。结论:紫檀芪预处理能减轻大鼠MI/RI,其机制可能与调控心肌细胞自噬、提高抗氧化能力,从而减轻心肌细胞损伤有关。

Pterostilbene inhibits myocardial ischemia reperfusion injury by regulating autophagy in rats

Objective:To observe the effects of Pterostilbene on myocardial ischemia/reperfusion injury(MI/RI)in rats,and explore whether its protective mechanism is related to the regulation of myocardial autophagy.Methods:72 SD rats were randomly divided into 6 groups(n=12),including sham operation group,model group,aspirin group,Pterostilbene low dose group,Pterostilbene medium dose group and Pterostilbene high dose group.MI/RI model was established 14 days after administration. The pathological changes of myocardial tissue were observed,the myocardial infarction size was determined,and the expression levels of autophagy signal-related proteins Atg5,Beclin1,LC3Ⅰ/Ⅱ and p62 in myocardial tissue were determined. The contents of lactate dehydrogenase(LDH),creatine kinase isoenzyme(CK-MB),malondialdehyde(MDA),superoxide dismutase(SOD),catalase(CAT)and glutathione peroxidase(GSH-Px)in blood were determined.Results:Myocardial histopathological examination indicated that myocardial fiber fracture and inflammatory response occurred in MI/RI group compared with sham group.Compared with model group,all treatment groups showed improvement.Compared with sham group,model group had increased myocardial infarction area,LDH and CK-MB,increased MDA,decreased SOD,CAT and GSH-Px,increased Atg5,Beclin1 and LC3Ⅰ/Ⅱ protein,and decreased p62(P<0.05).Compared with model group,myocardial infarction size,LDH and CK-MB decreased,MDA decreased,SOD,CAT and GSH-Px increased,protein expressions of Atg5,Beclin1 and LC3Ⅰ/Ⅱ decreased,and p62 increased in all treatment groups(P<0.05).Conclusion:The pre-treatment of Pterostilbene can reduce MI/RI in rats,and the possible mechanism may be related to the regulation of autophagy of cardiomyocytes and the improvement of antioxidant capacity,thus alleviating the injury of cardiomyocytes.