【摘 要】
：
[目的]研究酒精对布洛芬毒性的影响.[材料和方法]SD大鼠27只,♀,分为CMC-Na对照组、酒精组、布洛芬120mg/kg单独给药组、酒精-布洛芬120mg/kg联合给药组,CMC-Na对照组6只,其余各组每组7只,CMC-Na对照组和布洛芬单独给药组每日给予1ml/100g布洛芬混悬液,酒精组每日给予0.5ml/100g普通市售52.白酒,酒精-布洛芬联合给药组每日先灌胃给予0.5ml/100
【机 构】
：
中国医学科学院北京协和医学院新药安全评价研究中心 中国医学科学院北京协和医学院新药安全评价研究中心
【出 处】
：
中国毒理学会第七次全国毒理学大会暨第八届湖北科技论坛
论文部分内容阅读
[目的]研究酒精对布洛芬毒性的影响.[材料和方法]SD大鼠27只,♀,分为CMC-Na对照组、酒精组、布洛芬120mg/kg单独给药组、酒精-布洛芬120mg/kg联合给药组,CMC-Na对照组6只,其余各组每组7只,CMC-Na对照组和布洛芬单独给药组每日给予1ml/100g布洛芬混悬液,酒精组每日给予0.5ml/100g普通市售52.白酒,酒精-布洛芬联合给药组每日先灌胃给予0.5ml/100g普通市售52.白酒,30min后灌胃给予1ml/100g布洛芬混悬液,连续给药3天,给药前及给药结束时称重,每日给药后观察记录动物行为、外观、毒性反应及死亡情况,给药结束后,对存活动物解剖,进行血清生化、肝脏和肾脏的组织病理学检查.[结果]给药后,联合给药组先后出现步态不稳、活动减少、伏卧不动、毛色无光泽等,3只大鼠于D4死亡,单独给药组仅出现活动减少,1只大鼠于D4死亡；给药结束,联合给药组大鼠体重明显下降(15.9％↓),血清生化检查中,尿素、肌酐、碱性磷酸酶值的显著性升高,而单独给药组并不引起这些指标的显著性改变；联合给药组和布洛芬单独给药组均引起了总蛋白、球蛋白、白蛋白等反应肝脏合成蛋白质能力的指标的改变,并且与CMC-Na组比较有显著性差异；肾脏组织病理学检查表明,联合给药中出现点状肾小管上皮嗜酸性变性、肾盂间质小灶急性炎、蛋白管型等肾组织病理学上的改变,而布洛芬单独给药组仅一例出现肾盂处囊肿；肝脏组织病理学检查表明,布洛芬单独给药组与联合给药组均出现点状肝细胞嗜酸性变性与片状肝细胞坏死,联合给药组还出现片状肝细胞脂肪变性,同时,酒精给药组3例分别出现了点状肝细胞嗜酸性变性和不同程度的肝细胞水肿.[结论]在同等剂量下,与单独给药组相比,联用组出现了更为明显的肝肾毒性,说明酒精显著增加了布洛芬的毒性,并且在增加肝毒性方面,酒精与布洛芬具有协同作用,在肝细胞的嗜酸性变性、脂肪性变性至肝细胞坏死等一系列的病变过程中相互促进,但对于肾毒性增强的机制尚不明确,值得进一步研究和阐述.
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