SD大鼠重复给予大黄素甲醚肝毒性与遗传毒性研究

目的：综合重复给药毒性试验和遗传毒性试验，对大黄素甲醚研究潜在肝毒性及遗传毒性进行评价。方法：雄性Spargue-Dawley（SD）大鼠随机分为对照组（0.5%羧甲基纤维素钠）及大黄素甲醚低（6.5 mg·kg^-1）、中（65 mg·kg^-1）和高剂量组（650 mg·kg^-1），连续14 d经口灌胃给药；平行设甲磺酸乙酯（200 mg·kg^-1）遗传毒性试验阳性对照组。观察动物临床症状，分析体质量、血清生化指标、肝脏质量及病理学指标变化，并开展微核试验及彗星试验。结果：连续14 d给予SD大鼠大黄素甲醚，未见明确的与大黄素甲醚有关的肝毒性表现，且未检出其存在诱导SD大鼠肝细胞染色体损伤DNA断裂的作用。结论：当前试验条件下大黄素甲醚未见毒副反应剂量为650 mg·kg^-1。本研究为对大黄素甲醚潜在肝毒性的初步探索，建议延长给药时间并增加动物数量，以进一步明确其体内毒性。

Objective:To evaluate the potential hepatotoxicity and genotoxicity of physcion by performing jointed repeated-dose toxicity study and genotoxicity study.Methods:Male Sprague-Dawley (SD) rats were randomly divided into control (0.5% sodium carboxymethyl cellulose), low dose (6.5 mg·kg^-1 physcion), medium dose (65 mg·kg^-1 physcion) and high dose (650 mg·kg^-1 physcion) groups.Administration was through oral gavage for consecutive 14 days.A positive control group for genotoxicity study were used in parallel and administrated with ethyl methanesulfonate (200 mg·kg^-1).Clinical symptoms, body weight, serum biochemical examinations data, liver weight and histopathological examination results were analyzed, and the micronucleus test and comet assay were performed.Results:No definite hepatotoxicity associated with physcion were found in SD rats with repeated doses for consecutively 14 days.No chromosome damage nor DNA breakage effect on the hepatocyte was detected.Conclusion:Under the current condition, no observable adverse effect level for physcion is estimated at 650 mg·kg^-1.As a preliminary exploration of the potential hepatotoxicity of physcion, a study with extended administration period and increased animal number is recommended for identifying its in vivo toxicity.