苓桂术甘汤干预非酒精性脂肪肝病的药效学研究及作用机制探讨  

Pharmacodynamic study and mechanism of action of Linggui Zhugan Decoction in the intervention of Nonalcoholic fatty liver disease

作　　者：赵传志 丁慧敏 胡紫晴 都永勤 周兰[1] 周鹏[1] 王靓[1] ZHAO Chuan-zhi;DING Hui-min;HU Zi-qing;DU Yong-qin;ZHOU Lan;ZHOU Peng;WANG Liang(College of Integrative Medicine,Anhui University of Chinese Medicine,Hefei 230012,China)

机构地区：[1]安徽中医药大学中西医结合学院,安徽合肥230012

出　　处：《海南医学院学报》2024年第1期29-38,共10页Journal of Hainan Medical University

基　　金：安徽自然科学基金面上项目(2208085MH277)。

摘　　要：目的:通过体内动物实验探究苓桂术甘汤对非酒精性脂肪肝病的治疗效果,网络药理学及分子对接技术探究苓桂术甘汤干预非酒精性脂肪肝病的作用机制。方法:高脂喂养20周建立非酒精性脂肪肝病大鼠模型,将大鼠分为6组,正常组、模型组、辛伐他汀组(4 mg/kg)、苓桂术甘汤低剂量组(2.1 g/kg)、苓桂术甘汤中剂量组(4.2 g/kg)、苓桂术甘汤高剂量组(8.4 g/kg),观察苓桂术甘汤干预后的HE染色及油红O染色的肝脏形态学变化,酶标仪检测血清中谷草转氨酶、谷丙转氨酶、血脂四项水平。利用网络药理学结合分子对接筛选苓桂术甘汤干预非酒精性脂肪肝病潜在作用机制及靶点。结果:苓桂术甘汤可显著改善模型大鼠的谷草转氨酶、谷丙转氨酶水平(P<0.05);HE染色和油红O染色显示苓桂术甘汤显著降低模型组大鼠的肝脏脂质沉积;苓桂术甘汤可显著降低模型大鼠血脂四项水平(P<0.05);网络药理学筛选出关键靶点10个,关键信号通路5条;分子对接结果表明前20活性成分均对前十靶点有良好结合能力。结论:表明苓桂术甘汤对非酒精性脂肪肝病有调节血脂及改善肝组织病变作用,并初步验证了苓桂术甘汤对脂质代谢相关基因的调控作用。Objective:To explore the therapeutic effect of Linggui Zhugan Decoction on nonalcoholic fatty liver disease through in vivo animal experiments,and to explore the mechanism of action of Linggui Zhugan Decoction in the intervention of nonalcoholic fatty liver disease through network pharmacology and molecular docking technology.Methods:A rat model of non-alcoholic fatty liver disease was established after 20 weeks of high-fat feeding,and the rats were divided into six groups,normal group,model group,simvastatin group(4 mg/kg),low-dose group of Linggui Zhugan Decoction(2.1 g/kg),medium-dose group of Linggui Zhugan Decoction(4.2 g/kg),and high-dose group of Linggui Zhugan Decoction(8.4 g/kg),and the liver morphological changes of HE staining and oil red O staining after the intervention of Linggui Zhugan Decoction were observed,and the microplate reader detected aspartate aminotransferase,alanine aminotransferase,Four levels of blood lipids.Network pharmacology combined with molecular docking was used to screen the potential mechanism and target of Linggui Zhugan Decoction for the intervention of non-alcoholic fatty liver disease.Results:Linggui Zhugan Decoction significantly improved the levels of alanine aminotransferase and alanine aminotransferase in model rats(P<0.05).HE staining and oil red O staining showed that Linggui Zhugan Decoction significantly reduced liver lipid deposition in rats in the model group.Linggui Zhugan Decoction could significantly reduce the quadruplical levels of blood lipids in model rats(P<0.05).Network pharmacology screened out 10 key targets and 5 key signaling pathways;The molecular docking results showed that the first 20 active ingredients all had good binding ability to the top 10 targets.Conclusion:Linggui Zhugan Decoction has the effect of regulating blood lipids and improving liver tissue lesions in non-alcoholic fatty liver disease,and preliminarily verifies the regulatory effect of Linggui Zhugan Decoction on lipid metabolism-related genes.

关 键 词：网络药理学 分子对接 苓桂术甘汤 非酒精性脂肪肝 

分 类 号：R285[医药卫生—中药学]