基于网络药理学与“以药测证”挖掘非酒精性脂肪性肝病的证型、治法与方药  

The Syndromes,Therapeutic Method and Prescriptions of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and"Syndrome Differentiation by Effect of Drugs"

作　　者：穆杰 鲁法庭[1] 王东[1] 苏悦[1] 刘西洋[1] 冯全生[1] MU Jie;LU Fating;WANG Dong;SU Yue;LIU Xiyang;FENG Quansheng(Chengdu University of TCM,Chengdu 611137,China)

机构地区：[1]成都中医药大学,四川成都611137

出　　处：《西部中医药》2025年第3期1-9,共9页Western Journal of Traditional Chinese Medicine

基　　金：四川省青年基金项目(2024NSFSC1829,2025ZNSFSC1795);成都市卫生健康委员会联合创新专项(WXLH202402052);成都中医药大学青基人才专项(QJRC2024002)。

摘　　要：目的:探讨非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的证机、治法、方药,并验证预测的中药复方的有效性。方法:采用靶点数据集建立蛋白质-蛋白质相互作用(protein-protein interactions,PPI)网络、拓扑分析、反向药靶关系检索等方法,探讨NAFLD证型、方药。另将24只Wistar大鼠分为空白组(正常饲养)、高脂饮食组(high-fat diet,HFD)(给予高脂饲料)和中药组(在高脂饲料基础上以中药灌胃),每组8只,4周后检测体质量、肝质量、肝指数、内脏脂肪质量、体脂率、血清生化等,评价预测处方对NAFLD的治疗作用。结果:采用反向药靶关系网络预测、分析出NAFLD主要涉及14种不同的证型,可以将桑叶、金银花、沙棘、银杏叶、葛花作为底方,参考16种中药类别而选择药物,实验研究显示预测处方能够显著改善NAFLD病理。HFD组相较空白组大鼠体质量、肝重、肝指数、内脏脂肪质量、体脂率、血清谷草转氨酶(aspartate aminotransferase,AST)、谷丙转氨酶(alanine aminotransferase,ALT)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、游离脂肪酸(free fatty acid,FFA)及肝组织TG含量均升高(P<0.01),且中药组相较HFD组体质量、肝重、肝指数、内脏脂肪质量、体脂率、血清AST、ALT、TG、TC、FFA及肝组织TG含量均降低(P<0.05);HFD组相较空白组肝组织TG含量升高(P<0.01),病理切片显示肝内出现显著的气球样变、炎症细胞聚集及部分肝细胞坏死。结论:NAFLD主要与热、毒、风、痰、瘀、湿相关,涉及了14种不同的证型,治疗以清热、解毒、化痰、止痛、健脾、祛风立法,且结合动物实验验证了桑叶、金银花、沙棘、银杏叶、葛花为底方对NAFLD的治疗效果。Objective:To survey the pathogenesis,therapeutic methods and prescriptions of nonalcoholic fatty liver disease(NAFLD),and to verify the effectiveness of the predicted Chinese medicine compound.Methods:Protein-protein interaction(PPI),topology analysis and reversed herbal targets established by therapeutic targets database(TTD),were explored to discuss the pathogenesis and prescriptions of NAFLD.Male adult Wistar rats were employed as the subjects in the experiment,all 24 Wistar rats were allocated to the blank group,HFD group and herb group(n=8),the predicted therapeutic effects of the prescription on NAFLD were assessed by detecting body mass,liver weight,liver index,visceral fat mass,body fat percentage and serum biochemical examination.Results:Reverse drug target network was adopted to predict and analyze 14 syndromes of NAFLD,Sangye(Mori folium),Jinyinhua(Lonicerae japonicae flos),Shaji(Hippophae fructus),Yinxingye(Ginkgo Folium)and Gehua(Flower of lobed Kudzuvine)were used as the based prescription,16 herbal categories were consulted and chosen according to the symptoms,the experiments displayed that the predicted prescription could noticeably improve the pathology of NAFLD.When HFD group was compared with the blank group,body mass,liver weight,liver index,visceral fat mass,body fat percentage,and the contents of AST,ALT,TG,TC,FFA and TG in liver tissue were elevated(P<0.01),the decrease in body mass,liver weight,liver index,visceral fat mass,body fat percentage,and the contents of AST,ALT,TG,TC,FFA and TG in liver tissue was more evident in the herb group compared with HFD group(P<0.05);the content of TG was higher in HFD group than that of the blank group(P<0.01),pathological section showed significant balloon-like changes,inflammatory cell aggregation and partial hepatocyte necrosis in the liver.Conclusion:NAFLD is mainly related to heat,toxin,wind,phlegm,stasis and dampness,involving 14 various syndromes,treated with the methods of clearing heat,detoxifying,resolving phlegm,relieving pain,invigorating sp

关 键 词：非酒精性脂肪性肝病 网络药理学 反向药靶 以药测证 

分 类 号：R256.4[医药卫生—中医内科学]