摘要
目的探讨胆宁片(大黄、虎杖、青皮、白茅根、陈皮、郁金、山楂)对胆管结扎所致胆汁瘀积小鼠的保护作用及机制。方法将58只小鼠随机分为5组,分别为假手术组,胆管结扎模型组,胆宁片6、3、1.5 g/kg 3个剂量组,观察各组小鼠肝功能各项生化指标和肝组织病理学改变,并采用RT-PCR方法,检测多药耐药相关蛋白3(MRP3)、钠离子-牛磺胆酸协同转运蛋白(NTCP)、多药耐药蛋白2(MDR2)、谷胱甘肽-S-转移酶A1(GSTA1)和葡萄糖醛酸转移酶1A1(UGT1A1)mRNA水平的变化。结果与假手术组比较,胆管结扎模型组小鼠血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆红素(TB)、直接胆红素(DB)、总胆汁酸(TBA)、γ-三磷酸鸟苷(γ-GTP)均明显升高(P<0.01),组织病理学变化明显,NTCP表达明显降低(P<0.05),GSTA1,MRP3 mRNA表达明显升高(P<0.05或P<0.01),UGT1A1和MDR2表达未见明显变化。与模型组比较,胆宁片处理组可明显降低小鼠血清中ALT、AST、ALP、TB、DB的升高(P<0.05或P<0.01),且表现出剂量相关性。胆宁片6 g/kg剂量组可明显改善组织病理学变化,上调上述所有基因的mRNA表达(P<0.05或P<0.01)。但胆宁片各处理组对小鼠血清中TBA和γ-GTP无明显影响。结论胆宁片能有效改善胆管结扎小鼠的胆汁瘀积、肝功能及减轻病理损害,其作用机制可能与上调NTCP、MRP3、GSTA1、UGT1A1和MDR2的表达,减少胆汁酸在肝脏中的蓄积有关。
AIM To investigate the effect and mechanism of Danning Tablets（Rhei Radix et Rhizoma,Polygoni cuspidate Rhizoma et Radix,Citri reticulatae Pericaprium viride,Imperatae Rhizoma,Citri reticulatae Pericarpium,Curcumae Radix,Crataegi Fructus） on mice with extrahepatic cholestasis reproduced by bile duct ligation.METHODS Fifty-eight male ICR mice were randomly assigned into five groups： sham-operated group,bile duct ligation model group,Danning Tablets of 6,3,1.5 g/kg groups treated with bile duct ligation.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 multidrug resistance-associated protein 3（MRP3）,Na＋-dependent taurocholate co-transporting polypeptide（NTCP）,multidrug resistance protein 2（MDR2）,glutathione-S transferase A1（GSTA1）,Uridine diphosphate-5-glucuronosyltransferase 1A1（UGT1A1）.RESULTS Compared with sham-operated group,serum levels of alanine aminotransferase（ALT）,aspartate aminotransferase（AST）,alkaline phosphatase（ALP）,total bilirubin（TB）,direct bilirubin（DB）,total bile acid（TBA） and γ-glutamyl transpeptidase（γ-GTP） significantly increased in bile duct ligation model group（P0.01）.Pathological changes of hepatic tissue were obvious.The mRNA level of NTCP down-regulated（P0.05）.The expressions of GSTA1 and MRP3 up-regulated（P0.05 or P0.01）,and the expressions of UGT1A1 and MDR2 remained uninfluenced.Compared with bile duct ligation model group,Danning Tablets groups significantly decreased serum levels of ALT,AST,ALP,TB,DB（P0.05 or P0.01） in a dose-dependent manner.After Danning Tablets of 6 g/kg treatment,pathological injuries were relieved and the gene expressions of NTCP,GSTA1,MRP3,UGT1A1 and MDR2 were higher than those of bile duct ligation model group（P0.05 or P0.01）.Danning Tablets groups did not alter serum levels of TBA and γ-GTP.CONCLUSION Danning Tablets could improve liver function and relieve hepatic pathological damage of mice with bile duct ligation.Their mechanism may be related to up-regulate the mRNA expressions of MRP3,NTCP,MDR2,GSTA1,UGT1A1 in liver and attenuate the accumulation of bile acids in hepatocytes.
出处
《中成药》
CAS
CSCD
北大核心
2013年第7期1385-1389,共5页
Chinese Traditional Patent Medicine
基金
上海市科学技术委员会科研计划项目(10DZ1970200
12QH1402200)
上海市卫生系统优秀青年人才计划(XYQ2011061)
关键词
胆宁片
胆管结扎
肝外胆汁瘀积
转运体
Danning Tablets
bile duct ligation
extrahepatic chlolestasis
transporters
作者简介
王莉（1989-），女，硕士，主要从事中药药效物质基础研究。Tel：13917795435，E-mail：w119890117@126．com
通信作者：王峥涛（1956-），教授，博士，主要从事中药药效物质基础研究。Tel：（021）51322519，E-mail：wangzht@hotmail．com
