芝麻素预处理激活Akt/eNOS通路减轻大鼠心肌缺血-再灌注损伤

Sesamin Preconditioning Attenuates Myocardial Ischemia Reperfusion Injury in Rats Through Activation of Akt/eNOS Signaling Pathway

目的:观察芝麻素对大鼠心肌缺血-再灌注损伤的改善作用,并探讨其可能机制。方法:将50只大鼠随机分为正常对照组、假手术组、模型组及芝麻素高(160 mg/kg)、低(80 mg/kg)剂量组,每组10只,连续给药7 d。采用冠状动脉左前降支结扎40 min再灌注120 min的方法建立大鼠心肌缺血-再灌注损伤模型,比色法检测血清心肌肌钙蛋白Ⅰ(c TnⅠ)、乳酸脱氢酶(LDH)及血清和心肌组织总抗氧化能力(TAOC)、一氧化氮(NO)水平,并检测心肌组织Caspase-3活性;TUNEL染色法检测心肌细胞凋亡水平;Western blot法检测心肌组织内皮型一氧化氮合酶(eNOS)磷酸化水平、蛋白激酶B(Akt)蛋白磷酸化水平及超氧化物歧化酶(SOD)蛋白表达水平。结果:芝麻素预处理能明显改善缺血-再灌注所致大鼠心肌损伤,降低血清c TnⅠ、LDH水平,提高血清及心肌组织总抗氧化能力和NO水平(P<0.05或P<0.01),并能显著提高心肌组织SOD蛋白表达及Akt、eNOS蛋白磷酸化水平,降低Caspase-3活性,减少心肌细胞凋亡(P<0.05或P<0.01)。结论:芝麻素预处理能减轻缺血-再灌注所致大鼠心肌损伤,其机制与增强机体抗氧化能力、激活Akt/eNOS信号通路、增加NO合成,进而抑制心肌细胞凋亡有关。

Objective： To investigate the protective effect of sesamin on myocardial ischemia reperfusion injury in rats,and to study the possible mechanism. Methods： 50 SD rats were randomly divided into control group,sham operated group,model group,high-dose sesamin group（ 160 mg / kg） and low-dose sesamin group（ 80 mg / kg）,with 10 rats in each group. Rats in sesamin groups were administered intragastrically with sesamin for 7 d. Then all rats except those in sham operated group were subjected to myocardial ischemia-myocardial ischemia reperfusion injury model by coronary artery ligation for 40 min and subsequent reperfusion for 120 min. Serum cardiac troponin Ⅰ（ c TnⅠ） and lactate dehydrogenase（ LDH）,levels of total antioxidant capacity（ TAOC） and nitric oxide（ NO） in serum and myocardial tissues,Caspase-3 activity in myocardial tissues were detected by colorimetric assay. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Phosphorylation level of endothelial nitric oxide synthase（ eNOS） and Protein kinase B（ Akt）,protein expression of superoxide dismutase（ SOD） in cardiac tissue were determined by Western blot. Results： Pretreatment with sesamin significantly ameliorated myocardial injury in rats which induced myocardial ischemia and reperfusion injury by reduced levels of serum c TnⅠand LDH（ P〈0. 05 or P〈0. 01）. Supplementation with sesamin resulted in a significant increasing of total antioxidant capacity and NO level in serum and myocardial tissues and cardiomyocyte apoptosis（ P〈0. 05 or P〈0. 01）,and remarkable decrease the Caspase-3 activity in myocardial tissues and cardiomyocyte apoptosis（ P〈0. 05 or P〈0. 01）. Sesamin significantly up-regulated the protein expression of SOD in cardiac tissues,and the levels of phosphorylated eNOS and Akt increased notably（ P〈0. 05 or P〈0. 01）. Conclusion： Pretreatment with sesamin effectively ameliorated myocardial ischemia reperfusion injury in rats,and the mechanism might be related to enhancing its antioxidant capacity and the activation of Akt / eNOS signaling pathway and subsequent increase of NO synthesis and suppression of cardiac myocyte apoptosis.