基于网络药理学和实验探究清肝降浊方调控氧化应激及炎症治疗代谢相关脂肪性肝病机制OA
Exploration on the Mechanism of Qinggan Jiangzhuo Prescription in Regulating Oxidative Stress and Inflammation for Metabolic Related Fatty Liver Disease Based on Network Pharmacology and Experimental Research
目的 探讨清肝降浊方治疗代谢相关脂肪性肝病(MAFLD)的作用机制.方法 应用网络药理学相关数据库筛选清肝降浊方活性成分靶点及MAFLD疾病靶点,取二者交集靶点构建蛋白相互作用(PPI)网络,并进行GO富集分析及KEGG通路富集分析.采用高脂蛋氨酸限制胆碱缺乏饲料构建MAFLD大鼠模型,将大鼠分为空白组、模型组、水飞蓟宾组、清肝降浊方等效剂量组、清肝降浊方高剂量组,并予相应干预,连续8周,检测各组大鼠血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆固醇、三酰甘油、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇,采用HE染色及非酒精性脂肪性肝病活动度评分(NAS)评价肝组织病理学变化,ELISA检测肝组织肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β、IL-6、丙二醛、总超氧化物歧化酶(T-SOD)、过氧化氢酶(CAT)、谷胱甘肽(GSH),Western blot检测肝组织氧化应激-炎症相关蛋白表达.结果 网络药理学分析显示,清肝降浊方治疗MAFLD的主要活性成分包括槲皮素、山柰酚、木犀草素等,交集靶点富集分析显示清肝降浊方可能通过调控氧化应激-炎症通路相关的Akt/Nrf2/NFκB轴及其上下游靶点发挥治疗MAFLD作用.动物实验结果显示,清肝降浊方能降低MAFLD模型大鼠血清转氨酶水平,改善血清脂质谱表达,降低肝组织TNF-α、IL-1β、IL-6、MDA,升高T-SOD、CAT、GSH,下调肝组织Akt、IKKβ、NF-κB、Keap1蛋白表达,上调IκBα、Nrf2、HO-1蛋白表达,差异均有统计学意义(P<0.05,P<0.01).结论 清肝降浊方治疗MAFLD具有多靶点、多通路的特性,可能通过调控Akt/Nrf2/NFκB信号轴减轻氧化应激及炎症反应,从而发挥对MAFLD的治疗作用.
Objective To investigate the mechanism of Qinggan Jiangzhuo Prescription in the treatment of metabolic associated fatty liver disease(MAFLD)rats.Methods The active component targets of Qinggan Jiangzhuo Prescription and the disease targets of MAFLD were screened by using the network pharmacology related database.The protein-protein interaction network was constructed by taking the intersection targets of the two,and the GO enrichment analysis and KEGG pathway enrichment analysis were carried out.High-fat methionine restricted choline deficient diet was used to establish MAFLD rat model.The rats were divided into blank group,model group,silibinin group,Qinggan Jiangzhuo Prescription equivalent dosage group,Qinggan Jiangzhuo Prescription high-dosage group,and given corresponding intervention for 8 weeks.Serum alanine aminotransferase,aspartate aminotransferase,total cholesterol,triglyceride,high density lipoprotein cholesterol and low density lipoprotein cholesterol were detected in each group.HE staining and NAFLD activity score of nonalcoholic fatty liver disease were used to evaluate the pathological changes of liver tissue.The TNF-α,IL-1β,IL-6,MDA,T-SOD,CAT and GSH in liver tissue were detected by ELISA.The expressions of oxidative stress inflammation related proteins in liver tissue were detected by Western blot.Results Network pharmacology results showed that the core components of Qinggan Jiangzhuo Prescription included quercetin,kaempferol,luteolin,etc.,which may exert a protective effect on MAFLD rats by regulating the Akt/Nrf2/NFκB axis and its upstream and downstream targets related to the oxidative stress inflammation pathway.Animal experiment results showed that Qinggan Jiangzhuo Prescription could reduce serum transaminase levels,improve serum lipid mass spectrometry expression,lower TNF-α,IL-1β,IL-6,MDA and increase T-SOD,CAT and GSH in liver tissue of MAFLD rats,down-regulate the expressions of Akt,IKKβ,NF-κB and Keap1 in liver tissue,and up-regulated the expressions of IκBα,Nrf2 and HO-1,with statistical significance(P<0.05,P<0.01).Conclusion Qinggan Jiangzhuo Prescription has the characteristics of multi-target and multi pathway in the treatment of MAFLD.It may alleviate oxidative stress and inflammatory response by regulating the Akt/Nrf2/NFκB signaling axis,thereby exerting therapeutic effects on MAFLD.
周天惠;廖镜林;蒋婷;宋依蓬;许卫华;姚树坤
北京中医药大学,北京 100029北京中医药大学,北京 100029北京中医药大学,北京 100029北京中医药大学,北京 100029中日友好医院,北京 100029中日友好医院,北京 100029
医药卫生
清肝降浊方代谢相关脂肪性肝病氧化应激炎症Akt/Nrf2/NFκB信号通路网络药理学
Qinggan Jiangzhuo Prescriptionmetabolic related fatty liver diseaseoxidative stressinflammationAkt/Nrf2/NFκB signaling pathwaynetwork pharmacology
《中国中医药信息杂志》 2026 (4)
41-49,9
中日友好医院生物医学转化工程系列研究项目(PYBZ1815)北京市科技计划-G20工程创新研究(Z171100001717008)北京中医药大学教育科学研究课题(XBB24037)
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