现代中西医结合杂志2025，Vol.34Issue(16)：2191-2201,2320,12.DOI:10.3969/j.issn.1008-8849.2025.16.001
基于网络药理学及实验验证探讨降糖舒心方治疗糖尿病合并慢性心力衰竭的作用机制
Exploring the mechanism of action of hypoglycaemic Shuxin formula in the treatment of diabetes mellitus combined with chronic heart failure based on network pharmacology and experimental validation
摘要
Abstract
Objective It is to explore the effect and mechanism of hypoglycaemic Shuxin formula in the treatment of di-abetes mellitus complicated with chronic heart failure by using network pharmacology methods and experimental verification.Methods ①The active components of hypoglycaemic Shuxin formula and the related targets of diabetes mellitus complicated with chronic heart failure were retrieved from the network pharmacology database and related platforms,a PPI protein inter-action network was constructed,and GO and KEGG enrichment analyses were performed to build a network diagram of the compound drug-component-target-pathway.Molecular docking was conducted to verify the affinity between the top 5 active components with the highest Degree value among the core targets and the top 5 core targets with the highest Degree value in the PPI.②Fifty SD rats were randomly divided into control group,model group,western medicine group,low-dose hypo-glycaemic Shuxin formula group and high-dose hypoglycaemic Shuxin formula group,with 10 rats in each group.The con-trol group was fed with normal diet,while the other groups were intraperitoneally injected with streptozotocin once to estab-lish diabetic models,and then the chronic heart failure models were established by abdominal aortic ligation and high-fat di-et feeding.After the models of diabetes mellitus with chronic heart failure were successful established,the low-dose hypo-glycaemic Shuxin formula group was intragastrically administered with 1.0 g/(kg·d)of hypoglycaemic Shuxin formula so-lution,the high-dose hypoglycaemic Shuxin formula group was intragastrically administered with 1.5 g/(kg·d)of hypo-glycaemic Shuxin formula solution,the western medicine group was intragastrically administered with an equal volume solu-tion of benazepril 3.0 mg/kg and glimepiride 8.0 mg/kg,and the control group and model group were intragastrically ad-ministered with an equal volume of distilled water,all once daily,continuously gavaged for 2 months.The pathological morphology of myocardial tissue was observed by HE staining,and the serum levels of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were determined by ELISA,the positive protein expressions of TNF-α and IL-6 in myocardial tissue were detected by immunohistochemistry,and the protein expressions of serine/threonine pro-tein kinase 1(AKT1)protein in myocardial tissue were detected by Western blot.Results①A total of 171 active ingredi-ents,331 intersection targets,and 196 signaling pathways were retrieved;the core components were peristalone,kaempfer-ol,salvia quinone phenol I,ginsenoside Rh4 and pteroside of astragalus.The core targets were AKT1,tumor necrosis fac-tor(TNF),insulin(INS),tyrosine kinase(SRC)and epidermal growth factor(EGFR).The molecular docking results showed that the binding ability between the core component and the core target was good.②The semi-quantitative scores of myocardial cell injury,the serum levels of CRP,TNF-α and IL-6,the average optical density values of positive protein ex-pressions of TNF-α and IL-6 in myocardial tissue,and the relative protein expressions of AKT1 in each administration group were all significantly lower than those in the model group(all P<0.05),and all the above indicators in the high-dose hy-poglycemic Shuxin formula group were significantly lower than those in the western medicine group(all P<0.05).Con-clusion Hypoglycaemic Shuxin formula can alleviate myocardial tissue fibrosis in diabetes mellitus with chronic heart failure through multiple components and multiple targets,AKT1 was the most crucial core target,this results provide new research idea for further exploring hypoglycaemic Shuxin formula in the treatment of diabetes mellitus with chronic heart failure.关键词
糖尿病/慢性心力衰竭/网络药理学/分子对接/降糖舒心方/丝氨酸/苏氨酸蛋白激酶1/炎症因子Key words
diabetes mellitus/chronic heart failure/network pharmacology/molecular docking/hypoglycaemic Shux-in formula/serine/threonine protein kinase 1/inflammatory factors分类
医药卫生引用本文复制引用
申亚亚,符显昭..基于网络药理学及实验验证探讨降糖舒心方治疗糖尿病合并慢性心力衰竭的作用机制[J].现代中西医结合杂志,2025,34(16):2191-2201,2320,12.基金项目
国家自然科学基金资助项目(81960833) （81960833）
