海南医科大学学报2025，Vol.31Issue(16)：1240-1253,14.DOI:10.13210/j.cnki.jhmu.20241023.002
苓桂术甘汤干预高脂诱导大鼠心肌纤维化的作用机制研究
Mechanism of Linggui Zhugan Decoction in intervening high-fat-induced myocardial fibrosis in rats
摘要
Abstract
Objective:To study the effect and mechanism of Linggui Zhugan Decoction(LGZGD)in the intervention of high-lipid-induced myocardial fibrosis by using network pharmacology combined with in vitro and in vivo experiments.Methods:The network pharmacology method was used to screen the active ingredients and targets of LGZGD,the targets of myocardial fibrosis and metabolic cardiomyopathy were obtained,the GO function and KEGG pathway enrichment analysis of the common targets were carried out,and the PPI network and the active ingredient-core target association network of the intersecting targets were es-tablished.A rat model of hyperlipidemia induced by high-fat feeding was constructed,and after the intervention of LGZGD,myo-cardial injury and collagen fiber deposition were observed by H&E staining and Sirius red staining,the mRNA expression levels of MMP9,TGF-β,SMAD3,and SMAD7 in myocardial tissues were detected by RT-qPCR,and the expression levels of CollagenⅠ and Collagen Ⅲ in myocardial tissues were detected by immunohistochemical staining.A model of H9C2 cardiomyocyte injury induced by palmitic acid(PA)in rats was constructed,and the effects of LGZGD on the level of apoptosis and the mRNA expres-sion levels of MMP9,TGF-β,SMAD3,and SMAD7 were investigated by flow cytometry and RT-qPCR.Results:The net-work pharmacology analysis showed that a total of 103 active ingredients and 886 core targets of LGZGD were screened,including 12 core targets related to the diseases,and 245 enrichment pathways closely related to myocardial fibrosis caused by metabolic car-diomyopathy.Animal experiments showed that compared to the normal group,the myocardial tissue of the model group showed obvious myocardial cell arrangement disorder,partial breakage of myocardial fibers,and interstitial fibrosis,the content of Colla-genⅠ,Collagen Ⅲ and the ratio of CollagenⅠ/Collagen Ⅲ in myocardial tissue were significantly increased,the mRNA expres-sions of TGF-β,SMAD3,and MMP9 were significantly increased,and the mRNA expression of SMAD7 expression was signifi-cantly reduced(P<0.05).LGZGD significantly improved the cardiac injury after 8 weeks of intervention,and the content of Col-lagenⅠ,Collagen Ⅲ and the ratio of CollagenⅠ/Collagen Ⅲ in myocardial tissue,the mRNA expression of TGF-β,SMAD3,and MMP9 was down-regulated,and the mRNA expression of SMAD7 was up-regulated(P<0.05).Cell experiments showed that compared to the normal group,the apoptosis level of the PA group was significantly increased,and the mRNA expression of TGF-β,SMAD3,and MMP9 of H9C2 cardiomyocytes was significantly increased,while the mRNA expression of SMAD7 was significantly reduced(P<0.01);and compared to the PA group,LGZGD could down-regulate the mRNA expression of TGF-β,SMAD3,and MMP9 in H9C2 cardiomyocytes,up-regulate the mRNA expression of SMAD7,and significantly improve the lev-el of apoptosis(P<0.01).Conclusion:LGZGD can inhibit myocardial fibrosis in high-fat rats by interfering with the TGF-β/SMAD pathway in myocardial tissue.关键词
苓桂术甘汤/网络药理学/心肌纤维化/高脂血症Key words
Linggui Zhugan Decoction/Network pharmacology/Myocardial fibrosis/Hyperlipidemia分类
医药卫生引用本文复制引用
彭红艳,张文龙,郭露琴,王靓..苓桂术甘汤干预高脂诱导大鼠心肌纤维化的作用机制研究[J].海南医科大学学报,2025,31(16):1240-1253,14.基金项目
This study was supported by the Natural Science Foundation Project of Anhui Province(2208085MH277) 安徽自然科学基金面上项目(2208085MH277) （2208085MH277）
