Mechanism Of Guizhi Based On FXR Related Pathway In The Treatment Of ANIT-induced Intrahepatic Cholestasis In Rats

Part 1 Literature Study on the Law of Traditional Chinese Medicine in the Treatment of Jaundice.Objective: To analyze and summarize the rules of Chinese medicine for jaundice,and to analyze whether Xinwen medicine is a commonly used medicine for jaundice.Methods: Search Chinese literatures about jaundice in Chinese databases of China Knowledge Network,Wanfang and Weipu,and establish a database of jaundice medications.Unified standardization of synonymous and synonymous names of the medicines was used.After data preprocessing,frequency analysis and aggregation were used.Various data mining methods such as class analysis are used for data statistics.Results: It was found that bitter cold medicine was the main treatment for jaundice,followed by Xin Wen medicine.Conclusion: Xinwen medicine is also a commonly used medicine for jaundice,which provides some ideas for clinical treatment of jaundice.Part 2 Effect of Guizhi on Rat Model of ANIT-induced Intrahepatic Cholestasis and Its MechanismObjective: To establish a disease-binding model using "ANIT + drug",to study the effects of Guizhi on the expression of FXR,SHP,BSEP,UGT2B4 in rat models of intrahepatic cholestasis,to observe serum biochemical indicators,liver tissue pathological changes,and to explore the treatment of Guizhi Intrahepatic cholestasis and its mechanism.Methods: Forty male SD rats(200 ± 20g)were randomly divided into normal group,model group,ursodeoxycholic acid(UDCA)(60 mg ·kg-1)group,and cinnamon stick 60 mg · kg-1 for treatment.Group,Guizhi20 mg · kg-1 treatment group,5 groups,8 in each group.Except for the normal group and the model group,the other groups were administered gavage at a corresponding concentration of continuous aqueous solution of 0.005 m L · g-1,once a day for 7 d.The normal group and the model group were given the same weight of saline.The stomach was administered once a day for 7 days.Except for the normal group,the other groups were given an oral administration of 100 mg · kg-1 ANIT on the 5th day,and the rats were administered once a day for 3 days.Blood was taken from the abdominal aorta 24 hours after the last administration,and serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBi L),and total bile acid(TBA)levels were measured;rat liver tissues were taken 1.5 ~ 2 cm,fixed with 10% formaldehyde,paraffin-embedded sections,parallel HE staining,and analysis of FXR expression by immunohistochemistry(IHC);RNA and protein were extracted from rat liver tissues,and FXR m RNA expression and FXR downstream were detected respectively Expression of SHP,UGT2B4,and BSEP proteins related to bile acid synthesis,detoxification,and transport.Results: Compared with the normal group,serum biochemistry showed that the levels of ALT,AST,TBi L,and TBA in the model group were elevated(P <0.05).Immunohistochemistry showed severe liver pathological damage,decreased expression of FXR protein and m RNA,and protein The expression results showed that the expressions of SHP,UGT2B4,and BSEP proteins were all reduced(P <0.05).Compared with the model group,the drug group could reduce the levels of ALT,AST,TBi L,and TBA in rat serum to varying degrees(P <0.05),can improve the pathological damage of liver tissue to different degrees,increase the gray value of FXR protein,and can promote the expression of FXR m RNA and FXR,SHP,BSEP and UGT2B4 proteins to varying degrees(P <0.05).Conclusion: Guizhi can relieve ANIT-induced intrahepatic cholestasis in rats to a certain extent,reduce the pathological damage of hepatocytes,and reduce the levels of ALT,AST,TBi L,and TBA in serum.The mechanism may be carried out by interfering with the FXR-SHP,FXR-UGT2B4,and FXR-BSEP signal pathways.