基于"异病同治"理论的舒胸方治疗非酒精性脂肪肝大鼠的作用机制研究OA

This study established a rat model of non-alcoholic fatty liver disease(NAFLD)to investigate the therapeutic effects and mechanisms of Shuxiong Prescription(SXP)in regulating the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB p65(NF-κB p65)inflammatory signaling pathway in NAFLD rats.A NAFLD rat model was established by administering a customized high-fat diet for eight weeks.Following successful modeling,NAFLD model rats were randomly assigned to the following groups:NAFLD model group,positive drug group(atorvastatin group,0.9 mg·kg-1),low-dose SXP group(SXP-L,5.5 g·kg-1),medium-dose SXP group(SXP-M,11 g·kg-1),and high-dose SXP group(SXP-H,22 g·kg-1).Additionally,non-modeled SD rats served as a blank group,with 10 rats per group.After four weeks of continuous gavage administration,tissue was collected.In vivo studies required observation of general rat condition,measurement of body weight changes,calculation of liver index,determination of levels of serum total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),and assessment of liver function indicators including alanine aminotransferase(ALT),aspartate aminotransferase(AST),and alkaline phosphatase(ALP).Histopathology was assessed using hematoxylin-eosin(HE)staining.Lipid deposition was evaluated via oil red O staining,and fibrosis severity was measured via Masson's trichrome staining.The protein expression levels of TLR4,MyD88,and NF-κB p65 in liver tissue were determined by Western blot analysis.Results indicated that rats in the model group exhibited significantly poorer physical condition with overall higher body weight(P<0.05),significantly elevated ALT(P<0.01)and AST(P<0.05)levels,enlarged liver volume,yellowish rough surface appearance,and fatty degeneration observed via HE staining.Following treatment,rats in the NAFLD group exhibited hepatic steatosis accompanied by inflammation and ballooning degeneration of hepatocytes.NAFLD-activity score(NAS)significantly increased(P<0.01),with massive lipid deposition(P<0.001)and marked hepatic fibrosis(P<0.001)observed.The level of serum TG,TC,and LDL-C was significantly elevated(P<0.01),and the HDL-C level was significantly decreased(P<0.001).The liver index significantly increased(P<0.01).Serum ALT,AST,and ALP levels were significantly elevated(P<0.01).The level of interleukin(IL)-1β,tumor necrosis factor(TNF)-α,and nitric oxide(NO)in liver tissue was significantly increased(P<0.05,P<0.01),and the protein expression level of TLR4,MyD88,and NF-κB p65 was significantly elevated(P<0.001).Compared with the NAFLD group,the SXP-L,SXP-M,SXP-H,and atorvastatin groups all showed improved histopathological changes in NAFLD rats,reduced NAS scores(P<0.01),decreased lipid deposition(P<0.05,P<0.01),inhibited fibrosis(P<0.05,P<0.01),significantly decreased TG,TC,and LDL-C levels(P<0.05,P<0.01),elevated HDL-C levels(P<0.01),reduced liver index(P<0.05,P<0.01),significantly lowered serum TG,TC,LDL-C,ALT,AST,and ALP levels(P<0.05,P<0.01),elevated HDL-C levels(P<0.05),significantly reduced IL-1β,TNF-α,and NO levels(P<0.05,P<0.01),and downregulated hepatic TLR4,MyD88,and NF-κB p65 protein expression levels(P<0.05,P<0.01,P<0.001).Results confirmed that SXP improved lipid metabolism,reduced hepatic inflammatory damage,and restored liver function in high-fat diet-induced NAFLD rats via the TLR4/MyD88/NF-κB p65 pathway.