胆木浸膏糖浆对4日龄SD大鼠发育毒性的研究
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1.广东莱恩医药研究院有限公司;2.广州湾区生物医药研究院,广东莱恩医药研究院有限公司

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]:1.广东省药物非临床评价研究企业重点实验室(2023B1212070029);2. 广东省重大人才工程项目(2021TY060021)。[第一作者]:戴锦龙(1989-),男,硕士,兽医师,中国兽医病理师(ACVP),研究方向:毒性病理学。 E-mail:daijinlong@lewwin.com.cn。[通讯作者]:杨威,教授级高级工程师/博士、博士后导师,广州湾区生物医药研究院院长、广东省药物非临床评价与研究重点实验室主任、广东莱恩医药研究院有限公司董事长、总经理,Tel:18928860179,(020)87998690,E-mail:yangwei0719@163.com;S通讯地址:广州市从化经济开发区高技术产业园创业路65号。


A Study on the Developmental Toxicity of Dangmu Extract Syrup in 4-day-old SD Rats
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1.Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd.;2.Guangzhou Bay Area Institute of Biomedicine,Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd *;3.Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd *;4.Guangzhou Bay Area Institute of Biomedicine,Guangdong Lewwin Pharmaceutical Research Institute Co., Ltd

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    摘要:

    目的 系统考察胆木浸膏糖浆对4日龄(PND4)SD大鼠生长发育的影响及其毒性反应。方法 根据整窝设计法将128例PND2幼鼠随机分为阴性对照组和低、中、高剂量组,从PND4起经口给予纯水/胆木浸膏糖浆,1次/天,重复给药18天,停药后恢复观察15天。期间对各组动物一般状态、生长发育、神经反射功能、自发行为活动、血液学、凝血、血生化、免疫功能、生长激素及组织病理等指标进行检测。结果 给药期末(PND22),各剂量组动物脾脏重量和脏体系数均较对照组增加,组织病理学检查可见对照组动物脾脏脾小结未形成,各剂量组动物脾脏脾小结结构形成,体积较对照组大、数量多,且其变化程度存在剂量关系;给药结束恢复15天后,各组动物脾脏重量较给药结束同组动物随生长发育增加,组织病理学检查各组动物脾脏结构较给药结束发育更完整,脾小结结构明显,但各组间比较未见明显差异。以上变化与胆木浸膏糖浆含营养成分加快动物器官结构发育有关,无毒理学意义。其余检测结果未见明显异常。结论 胆木浸膏糖浆可使4日龄SD大鼠脾脏结构提前发育完善,未见明显毒性靶器官,临床研究时注意控制胆木浸膏糖浆的用药剂量,定期进行脾脏及相关血液、血生化指标监测。

    Abstract:

    Objective To systematically investigate the impact of Dangmu extract syrup on the growth and development of 4-day-old (PND4) Sprague-Dawley (SD) rats and its toxicological reactions. Methods PND2 pups were randomly divided into a negative control group and low, medium, and high dose groups according to the whole litter design. Starting from PND4, the animals were orally administered with pure water or Dangmu extract syrup once daily for 18 consecutive days, followed by a 15-day recovery observation period after cessation of medication. During this period, the general condition, growth and development, neurological reflex function, spontaneous behavioral activity, hematology, coagulation, blood biochemistry, immune function, growth hormone, and histopathology of the animals in each dose group were assessed. Results At the end of the medication period (PND22), spleen weight and visceral system number of animals in all dose groups were increased compared with negative control group. Histopathological examination showed that spleen nodules did not form in the negative control group, and spleen nodules of animals in all dose groups were formed, larger in volume and more in number than those in the control group, and the degree of change was dose-dependent. After 15 days of recovery after administration, spleen weight of animals in all groups increased with growth and development compared with animals in the same group after administration, and the histopathological examination showed that the spleen structure of animals in all groups was more complete than that after administration, and the spleen nodule structure was obvious, but there was no significant difference between groups. The above changes were related to the development of animal organ structure accelerated by the nutrients contained in the syrup, and had no toxicological significance. No significant abnormal changes were found in other test results. Conclusion The splenic structure of 4-day-old SD rats can be improved in advance with no obvious toxic target organs. In clinical study, attention should be paid to controlling the dosage of the syrups, and regular monitoring of spleen and related blood and blood biochemical indexes should be carried out.

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  • 收稿日期:2024-07-26
  • 最后修改日期:2024-11-11
  • 录用日期:2025-05-06
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