The Effect Of Swertiamarin On Lipopolysaccharide-induced Cholestatic Hepatocyte Membrane Transporters Mrp3and Mrp4in Rats

0bjectiveThe study by observing the effect of Swertiamarin on Lipopolysaccharide inducedcholestasis hepatocyte membrane transporters multidrug resistance-associated protein3(Mrp3) and multidrug resistance-associated protein4(Mrp4) in rats to evaluate theeffect of Swertiamarin for the treatment of cholestasis, and to provide an important newclues for clinical treatment.MethodsForty-five, male, SD rats,were divided into three groups(n=15per group): salinegroup,lipopolysaccharide+saline group and lipopolysaccharide+Swertiamarin group.Samples were collected16hours after intraperitoneal injection oflipopolysaccharide.Hepatic function indictors(AST,AST,TBIL) were detected bybiochemical instrument.The liver tissue was collected to observe its morphologicalchanges by HE straining.Membrane or nuclear protein and total RNA were extractedfrom the liver tissue of rats. Expressions of Mrp3,Mrp4and Pxr,Car at transcription andprotein levels were detected by Real-time PCR and Western blotting, respectively.Results1. Compared to the saline group, hepatic function indictors(AST,AST,TBIL) wereelevated obviously in LPS+saline group (p <0.05).But compared to LPS+salinegroup,hepatic function indictors(AST,AST,TBIL) were decreased obviously (p <0.05)in LPS+Swertiamarin group(p <0.05).2. Compared to LPS+saline group, Swertiamarin can significantly improve thehepatic function in rats.3. Compared to the saline group,the protein expression of hepatocyte membranetransporters Mrp3,MRP4and nuclear receptors Pxr, Car were increased in LPS+saline group (p <0.05).Compared to LPS+saline group, Swertiamarin couldsignificantly up-regulate the protein expression of Mrp3,MRP4and nuclear receptorsPxr, Car in cholestatic rat liver(p <0.05).4. Compared to the saline group,the mRNA expression of hepatocyte membrane transporters Mrp3,Mrp4and nuclear receptors Pxr, Car were increased in LPS+salinegroup (p <0.05).Compared to LPS+saline group, Swertiamarin could significantlyup-regulate the mRNA expression of Mrp3,Mrp4and Pxr, Car in cholestatic rat liver(p<0.05)ConclusionThe results found that Swertiamarin can significantly reduce the cholestatic liverinjury in rats induced by lipopolysaccharide.This may be associated with up-regulatedexpression of hepatocyte membrane transporters Mrp3and Mrp4,which may be relatedto the regulation of nuclear receptors Pxr and Car.At the same time,the proteinexpression of hepatocyte membrane transporters Mrp3and MRP4were also increasedin lipopolysaccharide-induced cholestatic rats.,which may speculate that hepaticmembrane transporters Mrp3and Mrp4can relieve liver damage as protective factor incholestatic rats.