基于网络药理学和斑马鱼模型探究复方益肝灵对非酒精性脂肪肝的保护作用及机制

Study on the Protective Effect and Mechanism of Compound Yiganling on Nonalcoholic Fatty Liver Based on Network Pharmacology and Zebrafish Model

目的 基于斑马鱼模型及网络药理学技术研究复方益肝灵对非酒精性脂肪肝的保护作用及机制。方法 采用硫代乙酰胺诱导斑马鱼建立非酒精性脂肪肝动物模型,以斑马鱼肝脏表型、病理组织切片和生化指标为评价指标,综合评价复方益肝灵对非酒精性脂肪肝的保护作用;并通过网络药理学技术对其潜在作用机制进行预测。结果 与模型组相比,复方益肝灵给药组幼鱼肝组织颜色较浅,能够缓解斑马鱼肝脏结构出现脂肪变性样“空泡”的现象和肝脏面积减小的趋势,能够呈剂量依赖性降低甘油三酯、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)含量,且高剂量的保护作用更为显著;网络药理学筛选得复方益肝灵潜在有效成分24个及其作用靶点135个。此外,蛋白互作(PPI)网络分析得SFJ12等核心成分和RELA等核心靶点并进行分子对接,显示核心成分靶点间具有较好的结合活性。结论 复方益肝灵对硫代乙酰胺诱导的非酒精性脂肪肝斑马鱼模型具有保护作用,作用机制可能与干预脂质代谢和动脉粥样硬化等过程相关。

OBJECTIVE To study the protective effect and mechanism of compound Yiganling on nonalcoholic fatty liver disease based on zebrafish model and network pharmacology technology.METHODS The animal model of nonalcoholic fatty liver disease was established in zebrafish by using thioacetamide.Taking zebrafish liver phenotype,pathological tissue sections and biochemical indicators as evaluation indicators,the protective effect of compound Yiganling on nonalcoholic fatty liver was comprehensively evaluated,and its potential mechanism was predicted by network pharmacology technology.RESULTS Compared with the model group,the liver tissue of the juvenile fish in the compound Yiganling group was lighter in color,which could alleviate the phenomenon of steatosis like“vacuoles”in the liver structure of zebrafish and the trend of liver area reduction.It could reduce the contents of triglyceride,ALT,and AST in a dose-dependent manner,and the protective effect of high dose was more significant.Twenty-four potential active components and 135 targets of compound Yiganling were screened by network pharmacology.In addition,the PPI interaction and network comprehensive analysis obtained core components such as SFJ12 and core targets such as RELA,and molecular docking was carried out.The results showed that the core components and targets had good binding activity.CONCLUSION Compound Yiganling has protective effect on thioacetamide-induced nonalcoholic fatty liver in zebrafish model,and the mechanism of action may be related to the intervention of lipid and atherosclerosis.