大黄素对胆汁淤积大鼠肝细胞转运体基因表达的影响  

Effect of emodin on transporter gene expression of hepatocytes in intrahepatic cholestatic rats

作　　者：周方[1] 许红梅[1] 

机构地区：[1]重庆医科大学儿童医院感染消化科,重庆400014

出　　处：《第四军医大学学报》2009年第22期2663-2666,共4页Journal of the Fourth Military Medical University

基　　金：重庆市卫生局科研基金(07-2-46)

摘　　要：目的:探讨大黄素对α-萘异硫氰酸酯(ANIT)致急性肝内胆汁淤积的保护作用及其机制.方法:采用ANIT灌胃制备大鼠急性肝内胆汁淤积病理模型.将32只大鼠随机分为正常对照组、正常+大黄素组、模型组、模型+大黄素组,观察各组大鼠肝功能各项生化指标和肝组织病理学改变,并采用实时荧光定量RT-PCR检测肝细胞膜上转运体基因胆盐输出泵(BSEP)、多药耐药相关蛋白2(MRP2)、钠-牛磺胆酸共转运蛋白(NTCP)、多药耐药蛋白2(MDR2)、多药耐药相关蛋白3(MRP3)和核受体法尼酯衍生物X受体(FXR)mRNA水平的变化.结果:模型组与正常对照组相比较,TB,DB,ALT,AST,ALP和TBA浓度明显增高(P<0.01),光镜下可见肝细胞变性和坏死、中性粒细胞浸润,在mRNA水平NTCP,FXR表达降低(P<0.01),MDR2,MRP3表达增高(P<0.01或P<0.05),而BSEP,MRP2表达差异无显著性.经大黄素治疗后TB,DB,ALT,AST,ALP和TBA均降低(P<0.01或P<0.05),组织病理学改变轻微,NTCP,MDR2,MRP3表达高于模型组(P<0.05),但BSEP,MRP2,FXR的表达与模型组相比较差异无显著性.正常+大黄素组与正常对照组相比较上述各项指标差异均无显著性.结论:大黄素对胆汁淤积型肝炎有保护作用,调节肝脏中与胆汁酸代谢相关的NTCP,MDR2,MRP3的表达以减少胆汁酸在肝脏中的蓄积可能是其退黄、恢复肝脏功能的作用机制之一.AIM：To investigate the effect and mechanism of emodin on acute intrahepatic choles-tasis in rats.METHODS：Acutecholestatic model in rats was induced by alpha-naphthylisothiocya-nate（ANIT）.Normal control group,emodin group without ANIT treatment,model group and emodin group with ANIT treatment were set up.Liver function and pathological changes of hepatictissue were examined.Real-time fluorescent quantitative RT-PCR was used to detect the mRNA levels of the hepatic transporter bile salt export pump（BSEP）,multidrug resistance-associated protein 2（MRP2）,Na＋/taurocholate cotransporting peptide（NTCP）,multidrug resistance protein 2（MDR2）,multidrug resistance-associated protein 3（MRP3）and the nuclear receptor farnesoid X receptor（FXR）.RESULTS：In the model group compared with the normal control group,the concentrations of serum total bilirubin（TB）,direct bilirubin（DB）,alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphatase（ALP）and total bile acid（TBA）were increased（P〈0.01）;inflammatory cell infiltration,hepatic cellular change and necrosis could be observed by light microscop;the genes expression of NTCP and FXR were down-regulated（P〈0.01）,the MDR2 and MRP3 were up-regulated（P〈0.01 or P〈0.05）.But the expression of BSEP and MRP2 could not be affected.However,by emodin treatment,the concentrations of TB,DB,ALT,AST,ALP and TBA were decreased（P〈0.01 or P〈0.05）;Only mild histopathological change in liver could be seen;the genes expression of NTCP,MDR2 and MRP3 were higher than those of the model group（P〈0.05）,but the expression of BSEP,FXR and MRP2 could not be affected.In emodin group without ANIT treatment compared with the normal control group,the changes of Liver function,histopathology and transporter genes were not significantly different.CONCLUSION：Emodin has a protective effect on hepatocytes and a restoring activity on cholestatic hepatitis.Mechanism of its action may be related to induce expressi

关 键 词：大黄素 胆汁淤积 转运体 动物模型 

分 类 号：R285.5[医药卫生—中药学]