miR-375-3p过表达调控Akt-eNOS信号通路促进心肌梗死大鼠心肌修复作用机制

The mechanism of miR-375-3p overexpression regulating Akt-eNOS signaling pathway to promote myocardial repair in rats with myocardial infarction

目的探究miR-375-3p过表达调控丝氨酸-苏氨酸激酶(Akt)-内皮型一氧化氮合酶(eNOS)信号通路促进心肌梗死(MI)大鼠心肌修复作用的机制。方法将大鼠分为假手术(sham)组、MI组、阴性对照(NC)组、miR-375-3p组,各10只。比较各组miR-375-3p相对表达、心功能指标[左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、短轴缩短率(FS)、左室射血分数(LVEF)]、心肌损伤标志物[乳酸脱氢酶(LDH)、肌钙蛋白(cTnT)I、脑钠肽前体(Pro-BNP)]、心肌梗死面积、心肌组织病理学变化及Akt、p-Akt、eNOS、p-eNOS蛋白表达。结果与sham组比较,MI组、NC组miR-375-3p表达显著降低;miR-375-3p组miR-375-3p表达显著高于sham组及MI组(P<0.05)。与sham组比较,MI组、NC组及miR-375-3p组LVEDD、LVESD及LDH、cTnTI、Pro-BNP显著升高,FS、LVEF及Akt、p-Akt、eNOS、p-eNOS蛋白表达显著降低,MI面积显著增加(P<0.05)。与MI组比较,miR-375-3p组LVEDD、LVESD及LDH、cTnTI、Pro-BNP显著降低,MI面积显著减少,FS、LVEF及Akt、p-Akt、eNOS、p-eNOS蛋白表达显著升高(P<0.05)。结论miR-375-3p过表达可激活Akt-eNOS信号通路促进MI大鼠心肌修复。

Objective To explore the mechanism of miR-375-3p overexpression regulating serine-threonine kinase(Akt)-endothelial nitric oxide synthase(eNOS)signaling pathway to promote myocardial repair in rats with myocardial infarction(MI).Methods The rats were divided into sham-operation(sham)group,MI group,negative control(NC)group and miR-375-3p group,with 10 rats in each group.The relative expressions of miR-375-3p,cardiac function indexes〔left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),short axis shortening rate(FS),and left ventricular ejection fraction(LVEF)〕,markers of myocardial injury〔lactic dehydrogenase(LDH),troponin(cTNT)I,brain natriuretic peptide precursor(Pro-BNP)〕,myocardial infarction size,myocardial histomathological changes,and protein expressions of Akt,p-Akt,eNOS and p-eNOS were com-pared among four groups,respectively.Results Compared with sham group,the expression of miR-375-3p in MI group and NC group was significantly decreased;the expression of miR-375-3p in miR-375-3p group was significantly higher than that in sham group and MI group(P<0.05).Compared with sham group,LVEDD,LVESD and LDH,cTNTI and Pro-BNP were significantly increased in MI group,NC group and miR-375-3p group,while the protein expressions of FS,LVEF and Akt,p-Akt,eNOS and p-eNOS were signifi-cantly decreased,the MI area was significantly increased(P<0.05).Compared with MI group,LVEDD,LVESD and LDH,cTNTI and Pro-BNP were significantly decreased,MI area was significantly decreased,and FS,LVEF and Akt,p-Akt,eNOS and p-eNOS protein expressions were significantly increased in miR-375-3p group(P<0.05).Conclusions Overexpression of miR-375-3p could activate Akt-eNOS signaling pathway and promote myocardial repair in MI rats.