摘要
目的研究木犀草素对心力衰竭大鼠心室重构的作用,以及对磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(PI3K/Akt/mTOR)信号通路的调控作用。方法以结扎左冠状动脉法配合节食与力竭式游泳制备慢性心力衰竭模型。SD大鼠称重后按体重编号以简单随机化法分为假手术组、模型组、木犀草素低剂量组和木犀草素高剂量组。检测各组大鼠心功能指标;比较血清B型利钠肽(BNP)水平和左心室质量指数(LVMI);HE染色观察心肌组织形态结构;Western blot检测心肌组织PI3K、Akt和mTOR表达情况。结果与模型组比较,木犀草素干预组的左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)和LVMI较小,左心室射血分数(LVEF)较大,BNP水平较低,PI3K蛋白相对表达量、p-Akt/Akt和p-mTOR/mTOR较高(均为P<0.05)。与木犀草素低剂量组比较,木犀草素高剂量组LVEDD、LVESD和LVMI更小,LVEF更大,BNP水平更低,PI3K蛋白相对表达量、p-Akt/Akt和p-mTOR/mTOR更高(均为P<0.05)。HE染色结果显示,模型组心肌细胞结构紊乱、心肌纤维断裂、间质血管充血;木犀草素干预组心肌细胞轻度充血、水肿,部分心肌纤维断裂,较模型组轻。结论木犀草素能改善慢性心力衰竭大鼠心功能,抑制心室重构,其机制可能与活化PI3K/Akt/mTOR信号通路有关。
Objective To explore the effect of luteolin on improvement of ventricular remodeling in rats with heart failure and the regulation of phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)signaling pathway.Methods The model of chronic heart failure(CHF)was established by ligating the left coronary artery,combined with diet and exhaustive swimming.After weighing,SD rats were divided into sham operation group,model group,luteolin low-dose group,and luteolin high-dose group by simple randomization method according to their weight numbers.The cardiac function parameters were detected.The levels of serum brain natriuretic peptide(BNP)and left ventricular mass index(LVMI)were compared.HE staining was used to observe the morphological structure of myocardium in each group.Western blot was conducted to detect the expression of PI3K,Akt and mTOR.Results Compared with the model group,the luteolin intervention group had smaller left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),and LVMI,higher left ventricular ejection fraction(LVEF),lower BNP concentration and higher PI3K protein relative expression,p-Akt/Akt,p-mTOR/mTOR level(all P<0.05).Compared with the luteolin low-dose group,the luteolin high-dose group had smaller LVEDD,LVESD,and LVMI,higher LVEF,lower BNP concentration,and higher PI3K protein relative expression,p-Akt/Akt,p-mTOR/mTOR level(all P<0.05).HE staining results showed that disordered myocardial cell structure,myocardial fiber rupture and interstitial vascular congestion were presented in the model group.Myocardial cells in the luteolin intervention group had less congestion and edema,and partial myocardial fibers breakage than model group.Conclusions Luteolin may improve heart function and inhibit ventricular remodeling in CHF rats,and the mechanism may be related to the activation of PI3K/Akt/mTOR signaling pathway.
作者
郑艳
刘艳辉
胡杰
李凌
Zheng Yan;Liu Yanhui;Hu Jie;Li Ling(Department of Cardiology,General Hospital of Yongmei Group,Yongcheng 476600,China;Department of Cardiology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450002,China)
出处
《中国心血管杂志》
2021年第2期169-173,共5页
Chinese Journal of Cardiovascular Medicine
基金
二○一四年度河南省医学科技攻关计划项目(201403026)。
