基于肠-肝轴探讨荣木复肝方对胆汁淤积小鼠的改善作用OA

AIM To explore the effects of Rongmu Fugan Formula on improving intestinal liver injury in mice with intrahepatic cholestasis(IC).METHODS Sixty male KM mice were randomly divided into blank group(0.1 mL/kg normal saline),model group[0.1 g/kg α-naphthyl isothiocyanate(ANIT)],oberoic acid(10 mg/kg oberoic acid)and Rongmu Fugan Formula low,medium and high dose groups(2.8,5.6 and 11.2 g/kg Rongmu Fugan Formula).Except for the blank group,the other groups of mice were given ANIT on the first day,and then the corresponding drugs were gavaged for 7 days,and the serum,liver and ileum were collected.Levels of serum liver function(ALT,AST,ALP,TBA,TBIL,DBIL)and lipid(TC,TG,LDL-C,HDL-C)were detected by biochemical method.HE staining and AB-PAS staining were used to observe the histopathology of liver and intestine.Immunohistochemistry and Western blot were used to detect the expression of key target protein farnesol X receptor(FXR)in ileal and liver tissues.Immunohistochemmistry was used to detect the expressions of cytokeratin 19(CK19)in liver tissue and Occludin in intestinal tissue,so as to observe the bile duct hyperplasia and intestinal barrier function.RT-qPCR was used to detect the expressions of bile acid transporters.RESULTS Compared with the blank group,the levels of serum ALT,AST,ALP,TBA,TBIL,DBIL,TC,TG and LDL-C in the model group increased(P＜0.01),while the HDL-C level decreased(P＜0.01).Bile duct cell proliferation and pathological damage in ileal and liver tissues were observed.The number of goblet cells and the expression of Occludin protein in ileal tissues decreased(P＜0.01).The expression of CK19 protein in liver tissue increased(P＜0.01).The expressions of FXR protein in liver and ileal tissues decreased(P＜0.01).The expressions of bile acid synthesis increased(P＜0.01)and the expressions of transporters decreased(P＜0.01).Compared with the model group,Rongmu Fugan Formula decreased the levels of serum ALT,AST,ALP,TBA,TBIL,DBIL,TC,TG and LDL-C(P＜0.05,P＜0.01)and increased the HDL-C level(P＜0.01).It also alleviated pathological damage in ileal and liver tissues;increased the number of goblet cells and the expression of Occludin protein in ileal tissue(P＜0.05,P＜0.01);decreased the expression of CK19 protein in liver tissue(P＜0.05,P＜0.01);increased the expression of FXR protein in liver and ileal tissues(P＜0.05,P＜0.01).It decreased the expressions of bile acid synthesis(P＜0.01)and increased the expressions of transporters(P＜0.05,P＜0.01).CONCLUSION Rongmu Fugan Formula exerts a protective effect against intestinal and liver injury in IC mice,and its regulatory mechanism may be associated with the nuclear receptor FXR.