四味土木香散通过调节miR-34a-5p/Notch1信号通路改善机械牵张诱导的H9c2心肌细胞肥大  

Siwei Tumuxiang Powder Ameliorates Mechanical Stretch-induced Hypertrophy of H9c2 Cardiomyocytes by Regulating the MiR-34a-5p/Notch1 Signaling Pathway

作　　者：李健英 魏明慧 鲁子瑜 蒋碧辉 张欣 薛明明 LI Jianying;WEI Minghui;LU Ziyu(School of Basic Medical Sciences,Inner Mongolia Medical University,Inner Mongolia 010059,China)

机构地区：[1]内蒙古医科大学基础医学院,呼和浩特010059

出　　处：《医学研究杂志》2024年第8期107-114,共8页Journal of Medical Research

基　　金：内蒙古自治区科技计划资助项目(2020GG0238);内蒙古自治区自然科学基金资助项目(2020MS08139,2022LHMS08002)。

摘　　要：目的探讨四味土木香散(siwei tumuxiang powder,STP)对机械牵张诱导的大鼠H9c2心肌细胞肥大模型的保护作用及作用机制。方法制备STP含药血清及细胞肥大模型,并筛选STP含药血清最适剂量与作用时间;检测H9c2心肌细胞中心房钠尿肽(atrial natriuretic peptide,ANP)、脑钠肽(brain natriuretic peptide,BNP)、miR-34a-5p及Notch1等因子的表达,验证STP是否通过调控miR-34a-5p/Notch1通路对H9c2心肌细胞起保护作用。结果STP含药血清干预模型细胞最适剂量为低剂量(0.972g/kg),作用时间为24h。STP降低了模型细胞中ANP、BNP、miR-34a-5p的表达(P<0.05)。转染miR-34a-5p mimic逆转了STP降低ANP、BNP表达的作用(P<0.05)。用siRNA法敲低Notch1逆转了STP降低ANP、BNP的表达(P<0.05)。Notch1为miR-34a-5p直接靶基因,miR-34a-5p降低了Notch1的表达(P<0.05)。STP干预后,Notch1、NICD1、Hes1蛋白表达降低(P<0.05);转染miR-34a-5p mimic逆转了STP降低Notch1、NICD1、Hes1蛋白表达的作用(P<0.05)。结论STP可能是通过影响miR-34a-5p表达负调控Notch1信号通路对机械牵张诱导的大鼠H9c2心肌细胞肥大发挥保护作用。Objective To investigate the protective effect and mechanism of siwei tumuxiang powder(STP)on the model of H9c2 cardiomyocytes hypertrophy induced by mechanical stretching in rats.Methods The STP drug-containing serum and the hypertrophic cell model were prepared,and the optimal dose and time of action of STP drug-containing serum were determined.The expressions of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),miR-34a-5p,Notch1 and other factors in H9c2 cardiomyocytes were detected to verify whether STP exerted a protective effect on H9c2 cardiomyocytes by regulating the miR-34a-5p/Notch1 pathway.Results The optimal dose(0.972g/kg)of STP drug-containing serum was low-dose,and the action time was 24 hours.STP decreased the expressions of ANP,BNP and miR-34a-5p in model cells(P<0.05).Transfection of miR-34a-5p mimic reversed the effect of STP on ANP and BNP expressions(P<0.05).Knocking down Notch1 by siRNA reversed the effect of STP on ANP and BNP expressions(P<0.05).Notch1 was the direct target gene of miR-34a-5p,and miR-34a-5p decreased the expression of Notch1(P<0.05).After STP intervention,the expression of Notch1,NICD1 and Hes1 proteins were decreased.Transfection of miR-34a-5p mimic reversed the effect of STP on the expressions of Notch1,NICD1 and Hes1 proteins(P<0.05).Conclusion STP exerts a protective effect on mechanical stretch-induced H9c2 cardiomyocyte hypertrophy by miR-34a-5p to negatively regulate the Notch1 signaling pathway.

关 键 词：心肌肥厚 四味土木香散 MiRNA-34a-5p Notch1信号通路 

分 类 号：R541[医药卫生—心血管疾病]