健肾颗粒急性毒性和长期毒性研究

Study on acute toxicity and long-term toxicity of Jianshen granules

目的:观察健肾颗粒大鼠经口给药可能出现的急性毒性、长期毒性反应,评价临床前安全性。方法:急性毒性试验:经口ig给药,空白对照组给予去离子水、受试物组给予健肾颗粒混悬液(24 g·kg^(-1)·d^(-1)),给药体积为30 mL·kg^(-1)·次^(-1),24 h内给药2次(分上、下午给予),给药后观察14 d,通过临床观察体重变化和病理大体解剖等确定急性毒性反应。长期毒性试验:经口ig给药,溶剂对照组给予超纯水,低、中、高剂量组给予0.025,0.100和0.300 g·mL^(-1)的健肾颗粒混悬液。试验给药26周,给药频率为bid,给药体积12 mL·kg^(-1)·次^(-1),恢复期4周。检查项目包括临床观察、体重、摄食量、血液学、生物化学和尿液分析检测、组织病理学检查等。结果:急毒试验:24 g·kg^(-1)健肾颗粒ig给予SD大鼠无明显急性毒性,最小致死剂量(MLD)>24 g·kg^(-1)。长毒试验:SD大鼠ig给予健肾颗粒重复给药26周,未观察到临床不良反应的剂量水平为2.4 g·kg^(-1)。高剂量组潜在毒性靶器官为肝脏和肾脏,主要毒性作用表现为7.2 g·kg^(-1)剂量对肝细胞空泡变性、肝细胞肥大和肾脏的肾小管玻璃小滴有促进作用,肾小管玻璃小滴恢复期未恢复。结论:健肾颗粒对受试动物在拟临床使用剂量范围内未见有明显的急性毒性和长期毒性作用。

Objective:To observe the possible acute toxicity and long-term toxicity of Jianshen granules in SD rats,and provide data for preclinical safety evaluation.Methods:A blank control group and a test group were set for acute toxicity experiment.The rats in the blank control group were given deionized water by gavage,and those in the test group were given Jianshen granules at the dose of 24 g·kg^(-1)·d^(-1) in a volume of 30 mL·kg^(-1) per time,twice in 24 h,and observation was performed for 14 d after administration.The acute toxicity was determined through observation of weight change and gross pathological anatomy.For long-term toxicity test,vehicle control group was given ultrapure water by gavage,and low,medium and high dose test groups were given 0.025,0.100 and 0.300 g·mL^(-1) Jianshen granule suspension for 26 weeks,at a frequency of twice a day in a volume of 12 mL·kg^(-1) per time.A recovery period of 4 weeks was followed.Test items include clinical observations,weight,food intake,hematology,biochemical and urinalysis tests,and histopathological examinations.Results:Jianshen granules at the dose of 24 g·kg^(-1) did not show significant acute toxicity in rats,and the minimum lethal dose(MLD)was greater than 24 g·kg^(-1).In the long-term toxicity test,the target organs of toxicity were the liver and kidney.The main toxic effects occurred at the dose of 7.2 g·kg^(-1),which included promotes hepatocyte hepatocyte vacuole degeneration,hepatocyte hypertrophy and renal tubule glass droplet.Conclusion:Jianshen granules have no obvious acute and long-term toxicity effects on the test animals in the clinical dose range.