荆防颗粒浸膏幼龄大鼠28天重复灌胃给药毒性研究

doi:10.19803/j.1672-8629.2022.05.09

摘要/Abstract

摘要： 目的探讨连续28 d重复灌胃荆防颗粒浸膏对刚离乳SD大鼠出现的毒性反应,为荆防颗粒浸膏在儿童患者中的应用提供参考。方法选用刚离乳SD大鼠144只,按照体重随机分为荆防颗粒浸膏1、3、10 g·kg^-1·d^-1 3个剂量组和空白对照组（注射用水0 g·kg^-1·d^-1）,每组36只,雌雄各半。动物按照15 mL·kg^-1的给药体积分别灌胃相应浓度的荆防颗粒浸膏和注射用水,每日1次,连续灌胃28 d,停药恢复28 d。试验期间,每日观察动物一般状态,每周2次检测动物体重和摄食量,雄鼠检查包皮分离时间、睾丸精子数量、血清睾酮,雌鼠检查阴道张开时间、动情周期和血清雌激素;; 给药期结束和恢复期结束分别对动物骨骼发育、神经系统功能、学习记忆、生长激素水平、免疫球蛋白水平、眼科学、血液学、血液生化学、尿液学和组织病理学进行检查。结果荆防颗粒浸膏各剂量组未见与受试物相关的异常体征,体重和摄食量无显著改变。10 g·kg^-1·d^-1组血液学指标白细胞（WBC）、中心粒细胞（NEUT）、淋巴细胞（LYMPH）、单核细胞（MONO）和血液生化学指标总蛋白（TP）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）、白蛋白（ALB）略有改变;; 且镜下观察脾脏可见“星空”现象。结论幼龄大鼠连续28 d灌胃荆防颗粒浸膏,未引起动物一般体征、体重、摄食量、性发育和性激素水平、生长发育等指标的异常改变,血液学及血生化学指标与组织病理学略有改变,但认为与受试物的毒性作用不相关。

关键词: 荆防颗粒浸膏, 幼龄大鼠, 重复给药, 安全性, 毒性

Abstract: Objective To investigate the toxicity of Jingfang granule extract on newly weaned SD rats after repeated intragastric administration for 28 days, so as to provide reference for the application of Jingfang granule extract in children. Methods A total of 144 newly weaned SD rats were selected and randomly divided into three dose groups of Jingfang granule extract 1, 3, 10 g·kg^-1·d^-1 and control group (water for injection 0 g·kg^-1·d^-1), 36 animals in each group, half male and half female. Animals were gavaged with Jingfang granule extract and water for injection at the corresponding concentration at an administration volume of 15 mL·kg^-1, once a day, for 28 d, and the drug was withdrawn and recovered for 28 d. During the experiment, the general state of the animals was observed daily, the body weight and food intake of the animals were detected twice a week, the time of foreskin separation, testicular sperm count, and serum testosterone was examined in male mice, and the time of vaginal opening, estrous cycle and serum estrogen were examined in female mice. At the end of the administration period and the end of the recovery period, the animal bone development, nervous system function, learning and memory, growth hormone level, immunoglobulin level, ophthalmology, hematology, blood biochemistry, urology and histopathology were examined respectively. Results There were no abnormal signs related to the test substance in Jingfang granule extract 1, 3 and 10 g·kg^-1·d^-1 groups, and there was no significant change in body weight and food intake. The hematological indexes WBC, NEUT, LYMPH, MONO and blood biochemical indexes TP, TG, TC, HDL-C, LDL-C and ALB in 10 g·kg^-1·d^-1 group changed slightly;; and the spleen observed under the microscope can see the "starry sky" phenomenon. Conclusion The administration of Jingfang granule extract to young rats for 28 days does't cause abnormal changes in general signs, body weight, food intake, sexual development, sex hormone level, growth and development and other indexes of animals. Hematological and biochemical indexes change slightly with histopathology, but not considered to be related to the toxic effects of the test substance.

Key words: Jingfang granule extract, young rat, repeated dosing, safety, toxicity

中图分类号:

R994.1

徐娇艳, 王恩力, 郁丽梅, 张伟, 孙颖, 张贵民. 荆防颗粒浸膏幼龄大鼠28天重复灌胃给药毒性研究[J]. 中国药物警戒, 2022, 19(5): 515-521.

XU Jiaoyan, WANG Enli, YU Limei, ZHANG Wei, SUN Ying, ZHANG Guimin. Toxicity of Jingfang granule extract by repeated gavage for 28 days in young rats[J]. Chinese Journal of Pharmacovigilance, 2022, 19(5): 515-521.

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