Caspase抑制剂F1013对刀豆蛋白A诱导小鼠急性肝损伤的治疗作用

Caspase抑制剂F1013对刀豆蛋白A诱导小鼠急性肝损伤
的治疗作用
邓利娟;李湛军;罗楹;范慧红
【期刊名称】《中国药理学通报》
【年(卷),期】2012(028)001
【摘要】目的研究Caspase抑制剂F1013对刀豆蛋白A(ConA)所致小鼠急性肝损伤模型的治疗作用,并对其机制进行初步探讨.方法 60只♂ BALB/c小鼠随机分成对照组、模型组、阳性药组(NAC 155 mg·kg-1)和F1013(5,2.5,1.25 mg·kg-1)给药组.除对照组外,其余组小鼠均尾静脉注射ConA建立小鼠急性肝损伤模型,造模后2 h,阳性药组腹腔注射NAC,F1013给药组和模型组分别皮下注射F1013和溶媒.造模后8 h留取血清检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(T-Bil)含量和TNF-α水平,肝组织进行HE染色,并检测肝细胞凋亡率.结果在ConA诱导小鼠急性肝损伤模型,F1013组均明显改善肝脏病理组织损伤;明显降低血清ALT、AST、T-Bil和TNF-α水平及肝细胞凋亡率(P<0.01或P<0.05).结论F1013对ConA所致小鼠急性肝损伤具有较好的治疗作用,其机制可能与减少TNF-α的产生及抗肝细胞凋亡有关.%Aim To investigate the therapeutical effect and the mechanism of F1013 on acute hepatic injury ( AHI) of mice induced by concanavalin A( ConA ). Methods 60 male BALB/c mice were randomly divided into groups, and were intravenously ( iv ) injected with ConA to induce AHI. 2 hours later, N-acetylc-steine ( NAC ) was intraperitoneally ( ip ) injected, and F1013 or solvent was subcutaneously ( sc ) injected. 8 hours after ConA injection, a single liver segment and
blood were taken for the histological analysis and the detection of hepatocellular apoptosis, alanine amin-otransferase ( ALT ), aspartate aminotransferase( AST ), total bilirubin ( T-Bil ) and tumor necrosis factor-a( TNF-a ). Results F1013 ( 5, 2. 5, 1. 25 mg ? Kg'1 ) effectively improved the live lesion, and markedly decreased the elevated serum levels of ALT, AST, T-Bil, TNF-a and inhibited hepatocyte apoptosis. Conclusions F1013 has a therapeutical effect on mice with AIH induced by ConA. This might be associated with reducing TNF-a level and the inhibition of cell apoptosis in liver tissue.
【总页数】4页(P136-139)
【作者】邓利娟;李湛军;罗楹;范慧红
【作者单位】中国食品药品检定研究院,北京,100050;中国食品药品检定研究院,北京,100050;上海睿星基因技术有限公司,上海,201203;中国食品药品检定研究院,北京,100050
【正文语种】中文
【中图分类】R-332;R329.25;R575.02;R575.05;R977.3
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