水芹总酚酸胶囊对Wistar大鼠的长期毒性研究

Long-term toxicity study the capsule of total phenolics acid extracted from Oenanthe Javanica in Wistar rats

目的:观察连续灌胃给予水芹总酚酸对Wistar大鼠的长期毒性反应,评价其长期用药的安全性,为拟定临床剂量提供实验依据。方法:Wistar大鼠160只,根据性别、体重随机分为对照组和高(3000mg/kg)、中(1500mg/kg)、低(750mg/kg)剂量组,每组40只,雌雄各半。每周灌胃6天(每周日停1天),连续给药26周。停药后留取部分大鼠进行4周恢复性观察。不同时段检查大鼠的一般症状、体重变化、耗料量、血液学指标、血清生化学指标。动物剖检后,称重主要脏器并计算脏器系数,进行组织病理学检查。结果:与同期对照组比较,水芹总酚酸750m g/kg、1500m g/kg剂量组动物各项检查均未见明显异常,开始出现毒性剂量为3000 mg/kg,主要毒性表现为体重增长缓慢,血液学检查NE%升高和LY%降低,上述毒性反应均于停药后4周内恢复正常。结论:水芹总酚酸对Wistar大鼠的安全剂量为1500 mg/kg,开始出现毒性剂量为3000 mg/kg,主要表现为对体重和血液学指标的影响,毒性反应可逆且程度较轻,未见延迟性毒性反应,建议临床使用时定期进行血液学指标检测。

Objective： To investigate the chronic toxicity damage of total phenolics acid extracted from Oenanthe javanica（ OJTPA） in rats,for evaluating its safety and providing a recommendation in defining its clinical dose. Method： Wistar rats（ n = 160） were randomly divided into four groups of 40 animals each（ 20 per sex）. They were administered with OJTPA 3000,1500,750m g /kg by gavage for 6 months followed by subsequent 1 month recovery period; 1% aqueous carboxymethylcellulose was used as the control. Mortality,clinical signs,body weight changes,food consumption,hematological and biochemical parameters,gross findings,organ weights and histological markers were monitored during the dosing and recovery periods. Result： Compared with normal control group,no significant differences were observed in rats,behaviors,food-intake,weight gain and related examination indexes among the 1500,750m g /kg groups. Began to appear toxic dose is3000 mg /kg,the main chronic toxical damage was the weight gained slowly,NE% increased and LY% decreased,but after recovery period observation,the toxicity was basically recovered. Conclusion： In general,OJTPA has a better safety. The NOAEL of OJTPA approximately is 1500 mg /kg,began to appear toxic dose is 3000 mg /kg,but the damage is reversible and can return to normal after withdrawal. We suggest that regular hematology index monitoring when OJTPA is clinically used.