中国药理学通报2026,Vol.42Issue(8):1453-1460,8.DOI:10.12360/CPB202510061
川芎嗪调控miR-29b-3p/Sirt1/p300/Yy1信号通路抑制缺氧心肌细胞sST2表达
Tetramethylpyrazine attenuates sST2 expression in hypoxic cardiomyocytes via miR-29b-3p/Sirt1/p300/Yy1 signaling axis
摘要
Abstract
Aim To investigate the inhibitory effect of tetramethylpyrazine(TMPZ)on the synthesis and se-cretion of soluble suppression of tumorigenicity 2(sST2)in hypoxic cardiomyocytes,and to elucidate its underlying molecular mechanism.Methods Pri-mary cardiomyocytes were isolated from neonatal rats,and a hypoxic cell model was established by using the oxygen-glucose deprivation(OGD)method.The lev-els of sST2 protein in the cell supernatant were mea-sured by ELISA.Upstream microRNAs(miRNAs)regulating Sirt1 was prediced using bioinformatic analysis,and the expression of miR-29 subtypes was verified by qRT-PCR.Cardiomyocytes were trans-fected with a miR-29b-3p mimic or inhibitor,and Sirt1 mRNA expression was detected by qRT-PCR.Follow-ing combined treatment with 10 μmol·L-1 TMPZ,the mRNA expression of miR-29b-3p,Sirt1,p300,Yy1,and sST2 was assessed by q RT-PCR.Results The ac-tive ingredients of Chuanxiong,namely TMPZ,sen-kyunolide I,and levistolide A,significantly reduced sST2 levels in hypoxic cardiomyocytes.Bioinformatic analysis predicted that Sirt1,a transcriptional suppres-sor of sST2,was negatively regulated by miR-29b-3p.In the hypoxic cardiomyocyte model,miR-29b-3p negatively regulated Sirt1 mRNA expression.Con-versely,TMPZ inhibited the expression of miR-29b-3p,upregulated Sirt1,decreased the mRNA levels of p300 and Yy1,and consequently reduced sST2 expres-sion.Conclusion TMPZ inhibits the synthesis and secretion of sST2 by downregulating miR-29b-3p ex-pression,thereby modulating the activity of the Sirt1/p300/Yy1 signaling pathway.关键词
川芎嗪/sST2/miR-29b-3p/Sirt1/缺氧心肌细胞/miRNAKey words
tetramethylpyrazine/sST2/miR-29b-3p/Sirt1/hypoxic cardiomyocytes/miRNA分类
医药卫生引用本文复制引用
王天宇,张锐,刘婷,智慧,陈萍,郭滢,刘琪,王虹..川芎嗪调控miR-29b-3p/Sirt1/p300/Yy1信号通路抑制缺氧心肌细胞sST2表达[J].中国药理学通报,2026,42(8):1453-1460,8.基金项目
国家自然科学基金资助项目(No 82274135) (No 82274135)
天津市教委科研项目(自然科学)(No 2023KJ143) (自然科学)
天津市自然科学基金资助项目(No 23JCYBJC00830) (No 23JCYBJC00830)