上海中医药杂志2026，Vol.60Issue(5)：34-47,14.DOI:10.16305/j.1007-1334.2026.z20250818003
基于代谢组学探讨苓桂术甘汤通过LPC-PPARα轴改善代谢功能障碍相关脂肪性肝炎的作用机制
Exploring mechanism of Linggui Zhugan Decoction in ameliorating metabolic dysfunction-associated steatohepatitis via LPC-PPARα axis based on metabolomics
摘要
Abstract
Objective To investigate the mechanism by which Linggui Zhugan Decoction(LGZG)alleviates methionine-choline-deficient(MCD)diet-induced metabolic dysfunction-associated steatohepatitis(MASH)via modulation of lysophosphatidylcholine(LPC)metabolism.Methods ①The chemical constituents of LGZG were identified using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS),and a"compound-target-pathway"network was constructed via network pharmacology to predict the key signaling pathways involved.②The MASH model SD rats were randomly divided into model group,LGZG group(16.56 g·kg⁻¹·d⁻¹),vitamin E group(40 mg·kg⁻¹·d⁻¹),and normal control group(n=6),with intervention for 4 weeks.The levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in rat serum,as well as the levels of triglycerides(TG)and total cholesterol(TC)in the liver were measured.Histopathological changes and lipid deposition of liver were assessed via hematoxylin-eosin(HE)and oil red O staining.Hepatic protein expression levels of peroxisome proliferator-activated receptor(PPAR)α,PPARγ coactivator 1α(PGC1α),carnitine palmitoyltransferase 1a(CPT1a),and major facilitator superfamily domain-containing protein 2a(Mfsd2a)were determined by Western blot.Hepatic metabolomics was employed to analyze alterations in the LPC metabolic profile.③ An AML12 hepatocyte lipid deposition model was established,and after intervention with LPC(18∶0),the cell viability was determined by the CCK-8 assay,while lipid deposition was evaluated by oil red O staining and TG content measurement.The activation effect of the PPARα pathway by LPC(18∶0)was validated using Western blot and a luciferase reporter gene assay.Results ①Network pharmacology analysis indicated that the PPAR signaling pathway is a potential key pathway for LGZG in treating MASH.②In vivo experiments showed that LGZG could significantly reduce the serum ALT and AST levels and hepatic TG level in the rats,as well as improve liver steatosis,inflammatory infiltration and NAS score.The mechanism is related to the upregulation of liver PPARα,PGC1a,and CPT1a protein expressions,as well as the increase in phosphorylated acetyl-CoA carboxylase(p-ACC)level.Metabolomics studies revealed that LGZG significantly reversed the downregulation of various LPCs in the liver of MASH rats.Among them,the level of LPC(18∶0)significantly increased,accompanied by the upregulation of the Mfsd2a transporter protein expression.Correlation analysis revealed a significant inverse relationship between hepatic TG levels and LPC(18∶0)content.③Cell experiments further confirmed that LPC(18∶0)could dose-dependently reduce the TG level in hepatocytes,activate PPARα transcriptional activity,and up-regulate CPT1a protein expression and the p-ACC/ACC ratio.Conclusions LGZG may promote the accumulation of endogenous LPC(18∶0)by regulating Mfsd2a,and then activate the PPARα signaling pathway,thereby improving the lipid metabolism disorder in MASH liver by promoting fatty acid β-oxidation and inhibiting lipid de novo lipogenesis.关键词
代谢功能障碍相关脂肪性肝炎/苓桂术甘汤/超高效液相色谱-串联质谱/网络药理学/代谢组学/脂质代谢/经典名方Key words
metabolic dysfunction-associated steatohepatitis/Linggui Zhugan Decoction/UPLC-Q-TOF/MS/network pharmacology/metabolomics/lipid metabolism/classic famous formula引用本文复制引用
王亦融,王雪,郭海婧,孙昀泓,戴亮,毛熙妍,王凯,季光,周文君..基于代谢组学探讨苓桂术甘汤通过LPC-PPARα轴改善代谢功能障碍相关脂肪性肝炎的作用机制[J].上海中医药杂志,2026,60(5):34-47,14.基金项目
国家自然科学基金项目(81620108030) （81620108030）
经方与现代中药融合创新全国重点实验室开放课题(LSLSKL20240130) （LSLSKL20240130）
国家资助博士后研究人员计划项目(GZB20250905) （GZB20250905）
