决明子冻干粉对SD大鼠的长期毒性研究

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摘要目的研究大鼠连续1年长期摄入决明子冻干粉的毒性，为人体食用提供参考依据。方法实验选用SPF级SD大鼠480只，雌雄各半。随机分为4组，每组120只。分别为：溶媒对照组（纯净水）、低剂量组（0.5 g生药/kg BW）、中剂量组（2.2 g生药/kg BW）、高剂量组（10.0 g生药/kg BW）。给药体积：1 mL/100 g，每周给药6 d，每天给药1次，连续给药52周，口服（灌胃）给药。每周进行体重和摄食量的测定。动物在给药第13、26、39、52周以及给药26、52周停药恢复4周后，各组分别剖杀20只，雌雄各半。进行血液学、血清生化学测定，剖解主要脏器进行脏器重量称量，计算脏器重量及脏器系数，并对各剂量组脏器进行组织病理学检查。结果 ①在整个试验周期中未发生因给予决明子药物本身引起的大鼠濒死和死亡的毒性反应。②各给药剂量组及对照组大鼠体重均增长，呈现出一定的剂量-反应关系。③大鼠连续灌胃给予决明子26周,中剂量、高剂量组雌性大鼠以及高剂量组雄性大鼠的总胆红素偏低（P < 0.01）,且恢复4周后，高剂量组雄性大鼠的总胆红素依旧偏低（P < 0.01）。给药39周后高剂量组雌性与雄性大鼠的总胆红素偏低（P < 0.05或P < 0.01）；给药52周后高剂量组雄性大鼠的三酰甘油比对照组显著性降低（P < 0.05），恢复4周后恢复正常。大鼠连续灌胃给予决明子26及39周，中剂量、高剂量组雄性大鼠的肾脏系数显著性高于对照组（P < 0.05或P < 0.01）。④SD大鼠连续灌胃决明子26、39、52周后，在高剂量组出现毒性的靶器官是肾脏，且肾脏毒性不可逆，在低剂量组和中剂量组未出现明显的毒性反应。结论本试验室条件下，决明子冻干粉的未发生毒性反应的剂量为2.2 g生药/kg BW，在高剂量（10.0 g生药/kg BW）下的毒性靶器官主要是肾脏。

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	魏若尧裴彦宇孙井江高虹

关键词 ：决明子冻干粉, 长期毒性, 未发生毒性反应的剂量, 毒性靶器官

Abstract：Objective To evaluate the chronic toxicity of Semen Cassiae freeze-dried powder in rats. Methods 480 SD rats were randomly divided into 4 groups (60 male and 60 female per group): control group (pure water), low-dose group (0.5 g/kg BW), mid-dose group (2.2 g/kg BW) and high-dose group (10.0 g/kg BW). The volume of drug for gavaging was 1.0 mL/100 g. animals were administrated with drug by 6 days every week for 52 weeks. Subsequently, the weight and foodintake were examined per week. Meanwhile, hematology, blood biochemistry, organ weight, organ coefficient and histopathology were detected on 13-week, 26- week, 39-week and 52-week, and stopping drug at the end of 26-week, 52-week following by 4 weeks recovery period with killing 20 rats in each group. Results ①The result showed there was no death case in each group. ②The weight of rats in dose groups and control group were increased, and it showed dose-related. ③Compared with the control group, the total bilirubin of male rats in mid-dose and high-dose group were lower after 26 weeks (P < 0.01), after recovery period the TBIL of male rats in high-dose group was still lower (P < 0.01). After 39 weeks treatment, the TBIL in high-dose group lower compared with the control group (P < 0.05 or P < 0.01); The triglyceride of male rats in high-dose group was lower after 52 weeks(P < 0.05) and returned to normal after recovered 4 weeks. On 26 weeks and 39 weeks, there were significant increased in relative kidney weights of male rats in mid-dose group and high-dose group compared with control group (P < 0.05 or P < 0.01). ④The toxic target organ in high-dose group was kidney on 26, 39, 52 weeks, and the toxicity was irreversible, no toxic showed in low-dose group and mid-dose group. Conclusion The no-observed-adverse-effect level for Semen Cassiae freeze-dried powder was 2.2 g/kg BW in rats, and the toxic target organ in high-dose (10.0 g/kg BW) group was kidney.

Key words： Semen Cassiae freeze-dried powder Chronic toxicity No-observed-adverse-effect level Toxic target organ

基金资助:国家中医药管理局中医药行业科研专项项目（201307012）。

通讯作者: 高虹（1968-），女，硕士，研究员，硕士研究生导师，主要从事药物临床前安全性评价研究。

作者简介: 魏若尧（1992-），女，中国医学科学院医学实验动物研究所2014级比较医学专业在读硕士研究生；研究方向：药物临床前安全性评价。

引用本文:

魏若尧裴彦宇孙井江高虹. 决明子冻干粉对SD大鼠的长期毒性研究[J]. 中国医药导报, 2017, 14(15): 4-9.
WEI Ruoyao PEI Yanyu SUN Jingjiang GAO Hong. Study on chronic toxicity of freeze-dried powdered Cassiae Semen in Sprague-Dawley rats. 中国医药导报, 2017, 14(15): 4-9.

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http://www.yiyaodaobao.com.cn/CN/ 或 http://www.yiyaodaobao.com.cn/CN/Y2017/V14/I15/4

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