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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 observe the long-term toxicities of total phenolic acids against Wistar rats by continuous intragastric administration and to evaluate the long-term safety of the preparations and to provide an experimental basis for the formulation of clinical doses. Methods: 160 Wistar rats were randomly divided into control group and high dose (3000mg / kg), middle dose (1500mg / kg) and low dose (750mg / kg), 40 in each group. Gavage 6 days a week (every Sunday for 1 day), continuous administration of 26 weeks. After stopping taking some rats for 4 weeks recovery. At different time intervals, the general symptoms, weight changes, consumption of materials, hematological indexes and serum biochemical indexes of rats were examined. After the autopsy, the main organs were weighed and the organ coefficients were calculated for histopathological examination. Results: Compared with the control group at the same period, no significant abnormalities were observed in all doses of 750 m g / kg and 1500 m g / kg of total phenolic acids, and the initial toxic dose was 3000 mg / kg. The main toxicity was weight gain Slow, hematological examination increased NE% and LY% decreased, the toxicity were normal within 4 weeks after withdrawal. Conclusion: The safe dose of total phenolic acids against Wistar rats is 1500 mg / kg, and the toxic dose begins to be 3000 mg / kg. The main effects of total phenolic acids on weight and hematological indexes are reversible and mild toxic reactions, No delayed toxic reactions, it is recommended for clinical use of hematology during regular testing.