中药新药与临床药理2025，Vol.36Issue(5)：657-665,9.DOI:10.19378/j.issn.1003-9783.2025.05.001
四逆散对胆汁淤积性肝损伤大鼠胆汁酸转运蛋白的影响
Effects of Sini San on Bile Acid Transport Proteins in Rats with Cholestatic Liver Injury
摘要
Abstract
Objective To investigate the effects of Sini San on bile acids and the expression of bile acid transport proteins in liver tissues of rats with cholestatic liver injury(CLI).Methods SD rats were randomly divided into a blank group,a model group,a ursodeoxycholic acid group(60 mg·kg-1),a high-dose Sini San group(3.78 g·kg-1),and a low-dose Sini San group(1.89 g·kg-1),with 6 rats in each group.The rats were orally administered once daily for 10 consecutive days.Except for the blank group,all other groups were orally administered α-naphthylisothiocyanate(ANIT)olive oil solution(100 mg·kg-1·d-1)on the fifth day to establish the CLI rat model.Serum biochemical indicators,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total bile acid(TBA),total bilirubin(TBIL),and direct bilirubin(DBIL),were measured.Liver histopathological changes were observed using HE staining.Bile acid content was detected by UHPLC-MS/MS.The mRNA and protein expression levels of multidrug resistance-associated protein 2(MRP2),multidrug resistance-associated protein 1(MDR1),multidrug resistance-associated protein 3(MDR3),Na+/taurocholate cotransporting polypeptide(NTCP),bile salt export pump(BSEP),and farnesoid X receptor(FXR)in liver tissues were detected by qRT-PCR and Western Blot.Results Compared with the blank group,the body mass of the model group rats significantly decreased(P＜0.05);serum levels of ALT,AST,ALP,TBA,TBIL,and DBIL significantly increased(P＜0.01);liver histopathological scores significantly increased(P＜0.01);the contents of TCA,T-β-MCA,and T-ω-MCA in liver tissues significantly increased(P＜0.05),while the contents of UDCA,ɑ-MCA,and β-MCA significantly decreased(P＜0.05,P＜0.01);the mRNA expression levels of FXR,MRP2,BSEP,NTCP,and MDR1 in liver tissues significantly decreased(P＜0.01),while the mRNA expression level of MDR3 significantly increased(P＜0.05);the protein expression levels of BSEP,NTCP,MDR3,MDR1,MRP2,and FXR in liver tissues significantly decreased(P＜0.05,P＜0.01).Compared with the model group,(1)the body mass of rats in all treatment groups significantly increased(P＜0.05),serum levels of ALT,AST,ALP,TBA,TBIL,and DBIL significantly decreased(P＜0.01),and liver histopathological scores significantly decreased(P＜0.01);(2)the contents of TCA and T-β-MCA in liver tissues of rats in all treatment groups significantly decreased(P＜0.05),the content of T-ω-MCA in liver tissues of rats in the high-and low-dose Sini San groups significantly decreased(P＜0.05),and the content of GLCA and ɑ-MCA in liver tissues of rats in the low-dose Sini San group significantly increased(P＜0.05,P＜0.01);(3)the mRNA expression levels of MRP2,NTCP,and MDR1 in liver tissues of rats in all treatment groups significantly increased(P＜0.01),the mRNA expression level of FXR in liver tissues of rats in the high-and low-dose Sini San groups significantly increased(P＜0.01),the mRNA expression level of BSEP in liver tissues of rats in the low-dose Sini San group significantly increased(P＜0.01),and the mRNA expression level of MDR3 in liver tissues of rats in the ursodeoxycholic acid group and the high-dose Sini San group significantly decreased(P＜0.05);(4)the protein expression levels of BSEP,MDR1,MRP2,and FXR in liver tissues of rats in all treatment groups significantly increased(P＜0.05,P＜0.01),the protein expression level of NTCP in liver tissues of rats in the ursodeoxycholic acid group and the low-dose Sini San group significantly increased(P＜0.01),and the protein expression level of MDR3 in liver tissues of rats in the high-and low-dose Sini San groups significantly increased(P＜0.01).Conclusion Sini San can improve liver histopathological damage and liver function indicators in CLI rats,promote bile acid excretion,and exert hepatoprotective and choleretic effects.Its mechanism may be related to regulating the expression of bile acid transport proteins and reducing bile acid levels.关键词
四逆散/胆汁淤积性肝损伤/胆汁酸转运蛋白/胆汁酸/保肝利胆/大鼠Key words
Sini San/cholestatic liver injury/bile acid transport proteins/bile acids/hepatoprotection and choleresis/rats分类
医药卫生引用本文复制引用
刘云帆,李颢玥,张梦杰,王雅静,曹娜娜,王茜..四逆散对胆汁淤积性肝损伤大鼠胆汁酸转运蛋白的影响[J].中药新药与临床药理,2025,36(5):657-665,9.基金项目
河北省自然科学基金中医药联合基金项目(H2022423305). （H2022423305）
