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OA

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.