摘要
目的 探讨川芎多糖(LCPS)对大鼠心肌缺血再灌注损伤(MIRI)及腺苷酸活化蛋白激酶(AMPK)/核因子红系2相关因子2(Nrf2)信号通路的影响.方法 将120只SD大鼠随机均分为假手术组、模型组、LCPS组、AMPK激动剂AICAR组和LCPS+AICAR组.除假手术组外,其他各组构建MIRI大鼠模型.超声影像系统检测各组心功能指标,ELISA法检测血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、心肌肌钙蛋白(cTnI)含量,计算心脏指数,TTC染色法检测心肌梗死面积,HE染色法观察心肌组织病理学改变,分光光度法检测丙二醛(MDA)和超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,Western blotting法检测心肌组织AMPK、磷酸化(p)-AMPK、Nrf2、血红素加氧酶-1(HO-1)蛋白表达.结果 LCPS能够明显改善MIRI大鼠心功能及心肌组织病变,减少心肌梗死面积,降低MDA、心脏指数以及血清LDH、CK-MB、cTnI水平,升高SOD、GSH-Px活性、p-AMPK/AMPK比值以及Nrf2、HO-1表达水平.LCPS联合AICAR对各指标的影响优于LCPS组和AICAR组(P＜0.05).结论 LCPS具有减轻大鼠MIRI的作用,其机制可能与激活AMPK/Nrf2信号通路、抑制氧化应激有关.
Abstract
Aim To investigate the effects of ligusticum chuanxiong polysaccharide(LCPS)on myocardial ischemia reperfu-sion injury(MIRI)and the roles of adenosine monophosphate-activated protein kinase(AMPK)/nuclear factor-erythroid 2-related fac-tor 2(Nrf2)signaling pathway in rats.Methods 120 SD rats were randomly divided into sham operation group,model group,LCPS group,AMPK activator AICAR group and LCPS+AICAR group.Except for the sham surgery group,other groups were used to construct MIRI rat models.The cardiac function indexes were detected by echocardiography,the content of creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),myocardial troponin(cTnI)in serum were determined by ELISA,the cardiac index was alculated;the myocardial infarction size was detected by TTC staining,the myocardial histopathological changes were observed by HE staining,the content of malondialdehyde(MDA)and the activity of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)were determined by spectrophotometry,and the protein expression of AMPK,phosphorylation(p)-AMPK,Nrf2,heme oxygenase-1(HO-1)were detected by Western blotting.Results LCPS can significantly improve cardiac function and myocardial tissue dam-age in MIRI rats,reduce myocardial infarction area,MDA levels,cardiac index,serum LDH,CK-MB,cTnI levels,increase SOD,GSH-Px activity,p-AMPK/AMPK ratio,and Nrf2 and HO-1 expression levels.The impact of LCPS combined with AICAR on vari-ous indicators is larger than that of the LCPS group and AICAR group(P＜0.05).Conclusion LCPS can reduce the MIRI in rats,and the mechanism may be related to the activation of AMPK/Nrf2 signaling pathway and the inhibition of oxidative stress.
维普
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