泽泻汤加味方长期毒性实验研究

Long-term Toxicity Experiment on Modified Zexie Tang

目的:观察泽泻汤加味方对Wistar大鼠产生的毒性反应及脏器损伤,确定毒性反应的剂量,为拟定人的安全用量提供参考。方法:Wistar大鼠80只,随机分为正常组,泽泻汤加味方低、中、高剂量组(15,30,60 g·kg-1),每组20只,雌雄各半。各组ig给药每日1次,连续90 d。每天观察记录动物体征;给药结束和停药2周后,分别对动物进行血液学和血清生化学指标检测;对主要脏器称重,计算脏器系数,进行病理组织学检察。结果:泽泻汤加味方对大鼠脏器系数未见异常。高剂量组大鼠活动减少、毛色发黄,脱毛;中、低剂量组雌性动物在第9,10周体重明显低于正常组(P<0.01,P<0.05)。高剂量组雌性动物在实验第10周体重明显低于正常组(P<0.05)。病理组织检查结果显示,泽泻汤加味方高剂量组大鼠雌雄各1例见肾小管上皮细胞水肿,坏死、脱落;雄性大鼠1例见肝脏瘀血。结论:泽泻汤加味方中剂量组90 d给药对大鼠未观察到明显有害作用,高剂量组可能出现一定的肝、肾损伤。泽泻汤加味方在较大剂量长期应用时密切关注可能引起的肝、肾毒性。

Objective： To observe the toxic reactions and organ injuries in wistar rats induced by modified Zexie Tang,determinate the dose of toxic reactions and provide reference for proposing the safe dosage in human beings. Method： Eighty Wistar rats were randomly divided into normal group and modified Zexie Tang low,middle and high dose groups（ 15,30,60 g·kg-1）,with 20 rats in each group,half male and half female.Rats were administered ig with this medicine once a day for 90 consecutive days. The animal signs were observed and recorded every day. Animal blood test and serum biochemical test were conducted at the end of administration and two weeks after drug withdrawal. The main organs of rats were weighed, organ index was calculated and histopathological examination was taken. Result： Modified Zexie Tang had no effect on organ index. Rats in high dose group had decreased activity,and their hair became yellow and slipping. Body weight of female rats in middle dose group and low dose group in 9thweek and 10 thweek was significantly lower than that in control group（ P〈0. 01,P〈0. 05）. Body weight of female rats in high dose group in 10 thweek was significantly lower than that in control group（ P〈0. 05）. Histopathological examination showed that edema,necrosis and falling off in renal tubular epithelial cells occurred in 1 male rat and 1 female rat in modified Zexie tang high dose group,and liver congestion occurred in one male rat. Conclusion： No obvious harmful effects were observed in rats of modified Zexie Tang middle dose group after 90 days of medication,but high dose group may have certain liver and kidney injury. Therefore,we shall pay close attention to the risks for liver and kidney toxicity in application of long-term and large dose of modified Zexie Tang.