天津中医药大学学报2026，Vol.45Issue(1)：55-65,11.DOI:10.11656/j.issn.1673-9043.2026.01.08
舒肝宁注射液调控FXR-MRP2/BSEP通路保肝、降酶及退黄机制研究
Study on the mechanism of Shuganning Injection in liver protection,enzyme reduction and jaundice regression via regulating the FXR-MRP2/BSEP pathway
摘要
Abstract
[Objective]To investigate the hepatoprotective,enzyme-lowering and jaundice-relieving effects of Shuganning Injection(SGN)in rats with septic intrahepatic cholestasis(IC),and to explore its underlying mechanisms.[Methods]Thirty-six male SD rats of SPF grade were randomly assigned to the following groups:Control(blank),LPS(model),Ursodeoxycholic Acid(UDCA),SGN-L,SGN-M,and SGN-H,with six rats per group.A septic IC model was established via intraperitoneal injection of LPS(5 mg/kg).The Control and LPS groups received tail vein injections of 10%glucose solution[6 mL/(kg•d)],while the UDCA group received intraperitoneal injections of UDCA[25 mg/(kg•d)].The SGN-L,SGN-M,and SGN-H groups received tail vein injections of SGN at 0.625,1.350,and 2.700 mL/(kg•d),respectively,administered continuously for 5 days.Collect rat bile and determine its flow rate.Biochemically measure total bile acids(TBA),total bilirubin(TBIL),direct bilirubin(DBIL),and reduced glutathione(GSH)in rat bile,alongside serum aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP)activity,and TBA,malondialdehyde(MDA),GSH,TBIL levels in serum.Enzyme-linked immunosorbent assay(ELISA)was employed to determine interleukin-6(IL-6),interleukin-1β(IL-1β),and tumour necrosis factor-α(TNF-α)concentrations in rat serum.Measurement of hepatic coefficients in rats,observation of pathological alterations via haematoxylin-eosin(HE)staining,determination of MRP2 expression levels by immunofluorescence(IF),and assessment of MRP2,BSEP,and FXR gene and protein expression levels via reverse transcription polymerase chain reaction(RT-PCR)and Western blot analysis.[Results]Compared with the LPS group,all SGN treatment groups exhibited improved hepatic tissue architecture,cellular morphology,and hepatic cord arrangement.Inflammatory cell infiltration,hepatocyte degeneration,and necrosis were reduced.Bile levels of GSH,TBA,TBIL,and DBIL increased,while serum AST,ALT,and ALP activities rose in rats.TBA,MDA,TBIL,IL-6,and IL-1β levels decreased,while GSH levels increased.MRP2 fluorescence intensity in liver tissue was enhanced(P<0.05 or P<0.01).In the SGN-H group,the hepatic coefficient decreased and bile flow accelerated,serum TNF-α levels decreased,and MRP2,BSEP,and FXR gene and protein expression levels increased in liver tissue(P<0.05 or P<0.01).[Conclusion]SGN ameliorates the severity of cholestasis and liver function in LPS-induced septic IC rats,alleviates inflammation,and exerts hepatoprotective,enzyme-lowering,and jaundice-reducing effects.Its mechanism may involve activating the FXR receptor in hepatocytes,thereby upregulating MRP2 and BSEP gene and protein expression to promote bile acid excretion.关键词
舒肝宁注射液/脓毒性肝内胆汁淤积/保肝/降酶/退黄/FXR-MRP2/BSEP通路Key words
Shuganning Injection/septic intrahepatic cholestasis/liver protection/enzyme reduction/jaundice regression/FXR-MRP2/BSEP pathway分类
医药卫生引用本文复制引用
刘张珍,吴世豪,任梦宇,王泽慧,朱金墙..舒肝宁注射液调控FXR-MRP2/BSEP通路保肝、降酶及退黄机制研究[J].天津中医药大学学报,2026,45(1):55-65,11.基金项目
贵州省科技计划项目(黔科合成果[2022]一般013). （黔科合成果[2022]一般013）
