中国药理学通报2011，Vol.27Issue(7)：1019-1023,5.DOI:10.3969/j.issn.1001-1978.2011.07.030
秋水仙碱肝损伤机制探讨
Study of the mechanism of liver injury induced by colchicin
摘要
Abstract
Aim To study the mechanism of liver injury induced by colchicin in SD rats. Methods 70 SD rats ( both sexs ) were randomized into 7 groups. After 28 days of administration of drugs respectively ,levels of serum biochemistry and histopathologic changes of liver tissues were determined. Multidrug resistance protein Ⅱ ( MRP2 ) protein expression was detected by immunostaining , while protein levels of farnesoid receptor ( FXR ) , cholesterol 7-α hydroxylase ( CYP7A1 ) . bile salt export pump ( BSEP ), were determined by Western blot. Result Compared with normal group, levels of serum ALT activity were significantly increased in colchicin groups. ALP activity and concentration of TBA also significantly increased . while HE straining showed that extensive focal necrosis , mono-nuclear cell inltration, extensive hepatocellular hydropic degeneration were induced, and protein level of CYP7A1 was upregulated , FXR , BSEP . MRP2 were downregulated in 6 mg · kg-1 group. ALP activity and concentration of TBA were not significantly changed , while extent of liver damage in total alkaloid extract of Colchicum autumnale L group ( 20 mg · kg-1 ) was lighter than that of colchicin group ( 6 mg · kg-1 ). Conclusion Compared with total alkaloid extract of Colchicum autumnale L, colchicin induced liver injury more severely. In the condition of liver injury, colchicin was similar in regulating synthesis and transportation of bile acid to 4-Acetamido phenol, inferred mainly colchicine induced liver injury caused by severe intrahepatic cholestasis.关键词
秋水仙/秋水仙碱/秋水仙总碱提取物/对乙酰氨基酚/肝损伤/肝内胆汁淤积分类
医药卫生引用本文复制引用
宋金萍,王涛,陈雪梅,杨洁,张富春,尚靖..秋水仙碱肝损伤机制探讨[J].中国药理学通报,2011,27(7):1019-1023,5.基金项目
国家科技支撑计划资助项目(No 2007BAI30B04),"十一五"科技重大专项资助项目(No 2009ZX09302-002) （No 2007BAI30B04）
