丝裂原活化蛋白激酶/细胞外信号调节激酶信号通路在穿心莲内酯治疗心肌缺血/再灌注损伤大鼠中的分子机制

目的:从丝裂原活化蛋白激酶/细胞外信号调节激酶(MAPK/ERK1/2)信号通路研究穿心莲内酯(AG)对心肌缺血/再灌注损伤(MI/RI)大鼠的分子机制,为AG能够安全地用于MI/RI的预防提供参考.方法:雄性SPF级SD大鼠60只,购入后先全部予适应性喂养2周,后将其随机分为假手术组、模型组、银杏内酯B干预组,AG治...

The molecular mechanism of MAPK/ERK1/2 signaling pathway in myocardial ischemia/reperfusion injury rats treated by andrographolide

Objective:Study on the therapeutic effect and mechanism of andrographolide(AG)on myocardial ischemia/reperfusion injury(MI/RI)in rats from MAPK/ERK1/2 signaling pathway.Methods:60 male clean SD rats were fed adaptively for 2 weeks after purchase,then they were randomly divided into sham operation group,model group,ginkgolide B intervention group,and andrographolide treatment group(low,middle,and high dose groups).After grouping,the corresponding drugs were given for 14 days and 14 days later,the MI/RI model was established by routine method(myocardial ischemia 30 min,reperfusion 120 min).Then blood samples were collected to detect the contents of lactate dehydrogenase(LDH),creatine kinase isoenzyme(CK-MB),and troponin I(cTnI).At the same time,myocardial histopathology,myocardial Ca²⁺-Mg²⁺-ATP activity,Na⁺-K⁺-ATP activity,malondialdehyde(MDA)content,and superoxide dismutase(SOD)content were measured.Finally,the expression of mitogen-activated protein kinase p38(p38-MAPK)and extracellular regulated protein kinase(p-ERK1/2)in the myocardium was detected by Western blot.Results:Myocardial HE staining showed that the myocardial cells in the sham operation group were uniform and arranged neatly.The myocardial fibers in the model group were extensively exercised,compared with the model group,the cells in the three treatment groups were significantly improved.Compared with the sham operation group,the model group serum LDH,CK-MB,cTnI,myocardial MDA,and p38-MAPK protein expression were significantly increased(P<0.05),myocardial SOD,Ca²⁺-Mg²⁺-ATP,Na⁺-K⁺-ATP,myocardial p-ERK1/2 protein expression were significantly decreased(P<0.05),compared with the model group,ginkgolides B group and andrographolide low,medium and high dose group for serum LDH,CK-MB,cTnI,myocardial MDA,and the protein expression of p38-MAPK was significantly decreased(P<0.05),and the SOD,Ca²⁺-Mg²⁺-ATP,Na⁺-K⁺-ATP, myocardial p-ERK1/2 protein were significantly increased(P<0.05).Conclusion:Andrographolide can effectively protect the myocardium and cardiac function of MI/RI rats,and its mechanism may be related to that andrographolide can regulate MAPK/ERK1/2 signal pathway.