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机构地区:[1]北京大学药学院分子与细胞药理学系,北京100083
出 处:《中国新药杂志》2006年第24期2123-2126,共4页Chinese Journal of New Drugs
摘 要:目的:研究阿嗪米特(azintamide)对豚鼠胆囊胆固醇结石的治疗作用。方法:用高胆固醇饮食诱发豚鼠胆囊胆固醇结石模型,进行胆囊结石计数;测定胆囊体积和胆囊胆汁量;测定血清总胆汁酸(TBA)、总胆红素(TBIL)、胆固醇(TCHO)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-C)、碱性磷酸酶(ALP);测定胆汁TCHO,TBA和TBIL。观察阿嗪米特(20和80mg·kg^(-1))对胆囊胆固醇结石的治疗作用。为探讨阿嗪米特抗胆囊胆固醇结石的作用机制,对胆囊壁组织进行了黏液素(mucin)的免疫组化实验。结果:与模型组比较,阿嗪米特20和80mg·kg^(-1)组成石率明显下降;胆囊体积和胆囊胆汁量显著减少;血清TCHO及LDL-C明显降低(P<0.05);胆汁TBA升高(P<0.05),胆汁TCHO及TBIL降低(P<0.05)。黏液素免疫组化实验中可观察到,模型组黏液素表达水平较高,而阿嗪米特组黏液素表达水平较低。已知利胆药熊去氧胆酸(UDCA)亦有显著效果。结论:阿嗪米特对高胆固醇饮食诱发的豚鼠胆囊胆固醇结石模型具有明显的治疗作用。Objective: To assess the effects of azintamide for guinea pigs with cholesterol gallstone. Methods: A model of cholesterol gallstone of guinea pigs was set up by feeding high cholesterol diets to guinea pigs. The effectiveness of azintamide (20 and 80 mg·kg^-1 ). in the treatment of cholesterol gallstones of guinea pigs was assessed based on the status of gallstone numbers, gallbladder volumes, bile and hematological examination pre- and post-administration of azintamide. The hematological examinations included serum TBA, TBIL, TCHO, TG, HDL-C, LDL-C and ALP, and bile biochemistry included bile volumes, TCHO, TBA and TBIL. The mucin levels in the gallbladder tissues were measured by the immunohistochemical assays. Results: The azintamide-treated guinea pigs experienced significant decreases of gallstone number, gallbladder volumes, bile volumes, serum TCHO, LDL-C,TCHO and TBIL ( P 〈0. 05 ) and increases of TBA ( P 〈0. 05 ). The guinea pigs receiving azintamide had less mucin levels than the normal guinea pigs. The known ursodeoxycholic acid (UDCA) showed similar outcomes. Conclusion: Azintamide was bioactive in the management of cholesterol gallstone of guinea pigs.
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