大黄素对肝内胆汁淤积大鼠P-gp表达的影响  

Effect of eomdin on P-gp expression 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,重庆400014

出　　处：《中国中药杂志》2010年第7期908-911,共4页China Journal of Chinese Materia Medica

基　　金：重庆市卫生局科研基金项目(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组、正常+大黄素组、模型组和模型+大黄素组,观察各组实验动物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检测肝细胞膜转运蛋白基因多药耐药蛋白1a(mdr1a)、多药耐药蛋白1b(mdr1b)和多药耐药蛋白2(mdr2)mRNA水平的表达,Western blot方法检测肝脏P-糖蛋白(P-gp)的变化。结果:模型+大黄素组与模型组比较,TBiL,DBiL,ALT,AST,ALP,TBA浓度明显降低(P<0.01或P<0.05);肝细胞变性和坏死、中性粒细胞浸润均减轻;在mRNA水平mdr1a,mdr1b,mdr2的表达均上调(P<0.01或P<0.05),P-gp表达同时也增高(P<0.05)。结论:大黄素对胆汁淤积型肝炎有保护作用,上调肝脏中与胆汁酸代谢相关的转运蛋白P-gp的表达以减少胆汁酸及其他有毒化合物在肝脏中的蓄积可能为其退黄、恢复肝脏功能的作用机制之一。Objective： To investigate the effect and mechanism of emodin on acute intrahepatic cholestasis induced by alpha-naphthyliso- thiocyanate（ANIT） in rats. Method： Acute cholestatic model in rats was induced by 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 hepatic tissue were examined.Real-time fluorescent quantitative RT-PCR was used to detect the mRNA levels of the hepatic transport protein genes mdr1a （multidrug resistance protein 1a）、mdr1b （multidrug resistance protein 1b）和mdr2 （multidrug resistance protein 2）, The expression of P-gp were determined by Western blotting analysis. Result： Compared to the model group, Emodin treatment resulted in significant reductions in serum total bilirubin（TBiL）, direct bilirubin （DBiL）, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） ,alkaline phosphatase （ALP）, total bile acid（TBA） （P〈0.01 or P〈0.05）. By examining the liver pathology,it was found that hepatic cellular change and necrosis, inflammatory cell infiltration and bile duct proliferation were notably alleviated in emodin model with ANIT treatment. Analysis of gene expression in livers from emodin-treated cholestatic rats revealed that mdr1a、mdr1b 和mdr2 could be up-regulated （P〈0.01或P〈0.05）, Expression of P-gp was increased in accordance with its mRNA（P〈0.05）. Conclusion： Emodin has a protective effect on hepatocytes and a restoring activity on cholestatic hepatitis. Mechanism of its action may be related to induce expression of the bile-metabolism-related transporter P-gp in the liver to prevent bile acids and other toxic compounds overaccumulation in hepatocytes and hepatic toxicity.

关 键 词：大黄素 胆汁淤积 mdrla mdrlb mdr2 P-糖蛋白 

分 类 号：R285.5[医药卫生—中药学]