首页|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

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

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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 Notch 1 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.
Siwei Tumuxiang Powder Ameliorates Mechanical Stretch-induced Hypertrophy of H9c2 Cardiomyocytes by Regulating the MiR-34a-5p/Notch1 Signaling Pathway
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 at-rial 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 de-creased 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 ex-pressions(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 mim-ic 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.

Myocardial hypertrophySiwei tumuxiang powderMiRNA-34a-5pNotch1 signaling pathway

李健英、魏明慧、鲁子瑜、蒋碧辉、张欣、薛明明

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010059 呼和浩特,内蒙古医科大学基础医学院

心肌肥厚 四味土木香散 MiRNA-34a-5p Notch1信号通路

2024

医学研究杂志
中国医学科学院

医学研究杂志

CSTPCD
影响因子:0.702
ISSN:1673-548X
年,卷(期):2024.53(8)