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作 者:刘宁[1] 刘威[1] 张丹[1] 鲍秀琦[1] 孙华[1]
机构地区:[1]中国医学科学院/北京协和医学院药物研究所,北京100050
出 处:《中国药物警戒》2017年第4期193-195,200,共4页Chinese Journal of Pharmacovigilance
基 金:国家自然科学基金面上项目(81173073):双环醇作用靶点研究及基于其骨架的新型治肝炎药物设计
摘 要:目的观察双环醇对α-萘异硫氰酸酯(ANIT)致小鼠淤积性黄疸的作用。方法 ICR小鼠连续灌胃给予双环醇200 mg·kg^(-1)5天,每天给药1次,在第3天给药后2 h单次灌胃给予ANIT 110 mg·kg^(-1),观察动物状态并继续给药。双环醇末次给药前动物禁食不禁水12 h,末次给药后2 h处理动物,计算肝脾指数,制备血清,全自动生化分析仪检测血清ALT、AST、ALP、TBIL、DBIL和TBA水平,制备10%肝匀浆,测定肝组织MDA和SOD含量。结果 ANIT可引起小鼠显著毒性和肝组织损伤,动物出现死亡,脾脏指数降低,血清转氨酶及胆红素、胆汁酸等含量显著升高,肝组织MDA含量升高,SOD降低。双环醇200 mg·kg^(-1)连续给药5次,能降低动物死亡率,改善脾脏指数,但对ANIT致小鼠血清肝功能生化指标升高无降低作用,进一步增大肝脏指数,且有进一步加重的趋势。结论双环醇有加重ANIT诱导的小鼠淤积性黄疸的作用,需引起注意。Objective To observe the effects o f bicyclol on a-naphthalene isothiocyanate (AMT) -induced liver injury in ICR mice. Methods ICR mice were given intragastric administration bicyclol 200 mg·kg-1 for five days continuously, oncedaily. Two hours after the third administration, the mice were treated with ANIT 110 mg·kg-1 to establish the liver damage model. All animals were killed on 2 h after the fifth bicyclol administration. The activities of ALT, AST, ALP, TBIL, DBIL and TBA in serum were measured by automatic chemistry analyzer. 10% liver homogenate were prepared to test the MDA and SOD. Results ANIT 110 mg.kg_1 could induce significant liver damage,the mortality rate of mice increased and the levels of serum ALT, AST, ALP, ALB, TBIL, DBIL and TBA were significantly increased. 200 mg·kg-1 bicyclol had no even aggravating effects on the elevated level of the blood biochemical indexes as well as MDA and SOD. Conclusion Bicyclol aggravates ANIT-induced liver injury in mice probably and this should catch our attentions.
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