时珍国医国药2026，Vol.37Issue(18)：3418-3425,8.DOI:10.70976/j.1008-0805.SZGYGY-2026-1803
基于PDGF通过RhoA/ROCK/HIF1α信号通路研究参竹心康方抗心肌纤维化作用机制
Mechanism of Shenzhu Xinkang Formula(参竹心康方)in anti-myocardial fibrosis via PDGF-mediated RhoA/ROCK/HIF1α signaling pathway
摘要
Abstract
Objective To investigate whether Shenzhu Xinkang Formula(参竹心康方,SZXKF)can ameliorate isoproterenol(ISO)-induced myocardial fibrosis(MF)in rats by regulating the platelet-derived growth factor(PDGF)-mediated Ras homolog gene family member A(RhoA)/Rho-associated coiled-coil kinase(ROCK)/hypoxia-inducible factor 1α(HIF1α)signaling pathway.Methods An MF rat model was established by subcutaneous injection of ISO.The MF model rats were randomly divided into the Control group,Model group,Enalapril maleate(Enalapril)group,and SZXKF(SZXK)group,with treatments administered for 4 weeks.Hematoxylin-eosin(HE)staining was used to observe histopathological changes in myocardial tissue.Masson's trichrome staining was performed to evaluate collagen fiber deposition in myocardial tissue.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of Collagen I and Collagen III in myocardial tissue.Quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR)was employed to detect the mRNA expression of PDGFRα in myocardial tissue.Western blot(WB)was conducted to assess the protein levels of α-smooth muscle actin(α-SMA),RhoA,ROCK1,ROCK2,and HIF1αin myocardial tissue.Results 1)Pathological staining results(HE and Masson):Compared to the Control group,myocardial cells in the Model group exhibited edema,significant enlargement in volume,and disordered arrangement,with markedly increased collagen deposition in the myocardial intersti-tial space.In contrast,both the Enalapril and SZXK groups showed significant improvement in cardiac pathological morphology com-pared to the Model group.2)ELISA results:Collagen I and Collagen III levels in myocardial tissue were significantly elevated in the Model group versus the Control group(P<0.05).Compared to the Model group,both the Enalapril and SZXK groups demonstrated sig-nificant reductions in Collagen I and Collagen III levels(P<0.05).3)qRT-PCR results:PDGFRαmRNA expression was significantly upregulated in the Model group compared to the Control group(P<0.05).In contrast,PDGFRαmRNA expression was markedly down-regulated in both the Enalapril and SZXK groups compared to the Model group(P<0.05).4)WB analysis:Protein expression levels of α-SMA,RhoA,ROCK1,ROCK2,and HIF1α were significantly increased in the Model group versus the Control group(P<0.05).Compared to the Model group,the Enalapril group showed significant reductions in RhoA,ROCK1,ROCK2,and HIF1α protein expression(P<0.05),but no significant difference in α-SMA expression(P>0.05).The SZXK group exhibited significant decreases in α-SMA,RhoA,ROCK1,ROCK2,and HIF1α protein levels(P<0.05).Conclusion SZXKF exerts anti-MF effects by downregulating PDGF to inhibit the RhoA/ROCK/HIF1α signaling pathway,thereby reducing excessive collagen fiber deposition in myocardial tissue of fibrotic rats.关键词
参竹心康方/心肌纤维化/PDGF/RhoA/ROCK/HIF1α通路Key words
Shenzhu Xinkang Formula(参竹心康方)/Myocardial fibrosis/PDGF/RhoA/ROCK/HIF1α pathway分类
医药卫生引用本文复制引用
朱辰瑶,赵启,赵文博,喻正科,颜旭,陈志红,庄红,汤济源,王凯丽,李媛彬,朱筱婧..基于PDGF通过RhoA/ROCK/HIF1α信号通路研究参竹心康方抗心肌纤维化作用机制[J].时珍国医国药,2026,37(18):3418-3425,8.基金项目
国家自然科学基金青年基金(82200333) （82200333）
湖南省卫生健康委重点课题(C202319018666) （C202319018666）
湖南省自然科学基金(2025JJ80806) （2025JJ80806）
