余甘方通过促进脂质自噬改善非酒精性脂肪肝的机制研究OA

Objective To investigate the mechanism by which Yugan Formula(余甘方,YGF)alleviates non-alcoholic fatty liver dis-ease(NAFLD)in mice.Methods Forty-five C57BL/6J mice were divided into the following groups:control,model,and YGF low/medium/high-dose.The liver index,oral glucose tolerance(OGTT),and insulin tolerance(ITT)were assessed.Serum levels of TG,TC,LDL-C,HDL-C,FFA,ALT,and AST were measured.Hepatic pathological changes were observed by HE and Oil Red O stain-ing.The protein expression levels of ACC,PLIN2,CPT1A,LC3B,p62(SQSTM1),Beclin-1,and Atg5 were determined by Western blot(WB).The mRNA expression levels of Lc3b,p62,Atg5,and Beclin-1 in the liver were measured by RT-qPCR.Results Com-pared with the control group,the model group showed significant increases in area under the curve of OGTT and ITT,serum levels of LDL-C,TG,TC,FFA,ALT,and AST(P<0.001),and a significant decrease in HDL-C(P<0.001).Furthermore,the model group exhibited upregulation of ACC and PLIN2 proteins,and downregulation of CPT1A protein(P<0.001).The protein and mRNA levels of autophagic markers LC3B,Atg5,and Beclin-1 were decreased,while p62 levels were increased(P<0.001),suggesting impaired lipo-phagy.Compared with the model group,YGF treatment at medium and high doses significantly reversed these alterations(P<0.05,P<0.01,or P<0.001).Specifically,YGF upregulated the protein expression of CPT1A,LC3B-II,Atg5,and Beclin-1,and downregu-lated ACC,PLIN2,and p62 protein.Concurrently,it downregulated the mRNA expression of Sqstm1(p62)(P<0.05,P<0.01,or P<0.001).Conclusion YGF alleviates NAFLD in mice by modulating glycolipid metabolism and promoting lipophagy.