目的 观察连续灌胃鸦胆子水提组分对大鼠的长期毒性,对其毒性定性、定位、定量以及与时间、剂量的相关性进行研究,明确毒性是其药效的延伸还是中药的自身毒性,以评价其长期用药的安全性.方法 80只Wistar大鼠随机分为鸦胆子水提组分高、中、低剂量组和正常对照组,大鼠连续灌胃鸦胆子水提组分27天,给药期间,每天观察动物的一般状况,每三天记录一次体重、日食量、日水量.停药后1天、27天分别检测血常规、血生化,测定主要脏器脏体比值并做病理组织检查.结果 鸦胆子水提组分灌胃27天可轻度影响大鼠的饮食和体重;对血常规无明显影响;血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平及肌酐(Cr)、尿素氮(BUN)含量均有所升高;心体比值、肾体比值也有所升高;高、中剂量组部分出现肾小球萎缩、肾小管玻璃样变等病理组织学变化.停药后27天除高剂量组血清Cr,BUN含量仍明显高于正常对照组外其他毒性改变均已恢复.结论 鸦胆子水提组分长期给药可对大鼠造成明显的肾毒性,且呈现明显的"时-毒"和"量-毒"关系,停药后毒性部分可逆.%Objective To observe the long-term toxicity of water extract of Fructus Brucea in rats and evaluate its safety of long-term medication. Methods 80 Wistar rats were randomly divided into high dose group, middle dose group,low dose group and normal group. The rats were consecutively drenched water extract of Fructus Brucea for 27 days. The general status of the animals was observed daily in medication duration and body weight, daily appetite,daily water quantity were recorded every 3 days. All animals were sacrificed on the 1 day and 27 day after discontinuation and blood routine, blood biochemistry were detected. Ratio of viscera to body was measured and the major organs were examined by the pathology. Results The diet and weight of rats were lightly reduced after a long time of administration. The blood routine was changed littlely while the activities of ALT, AST and contents of Cr, BUN in Crased. Ratio of heart and kidney to body in Crased also. Analosis of acinus renis and hyalinization of nephric tubule occuered to several rats of high and middle dose groups. Conclusion Obvious nephrotoxicity can be caused to rats by long-term administration of water extract of Fructus Brucea and the toxicity was partial reversible after discontinuation.
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