小鼠FOB安全药理学评价技术的构建与应用

Construction and application of the functional observation battery for safety pharmacology evaluation in mice

关键词:  小鼠  FOB  安全药理学  中枢神经系统

Key words:  Mice  functional observation battery (FOB)  safety pharmacology  central nervous system (CNS)

摘要:

目的 构建并应用一种小鼠功能观察组合（FOB）试验技术，评估药物对中枢神经系统（CNS）功能的影响，为安全药理学评价提供科学依据。方法 选取20只检疫合格的ICR小鼠，雌雄各半。根据性别和体重，采用分层随机法分组成溶媒对照组和盐酸氯丙嗪组，分别单次灌胃给予0.9%氯化钠注射液和25 mg/kg的盐酸氯丙嗪溶液。于给药前和给药后1 h、6 h和24 h进行FOB试验，包括笼内观察、旷场观察、接触观察、操作观察和特殊观察。观察指标涵盖自主神经调控、运动控制与反射、情绪与行为、中枢整合功能四个维度共64项指标。量化评分后系统考察药物对小鼠CNS功能的影响。结果 相较于溶媒对照组，盐酸氯丙嗪组动物在给药后1 h至6 h，观察指标四个维度均出现显著改变，而在给药24 h后基本恢复正常水平。结论 构建的小鼠FOB试验技术，可作为CNS功能安全药理学评价的有效工具。

Abstract:

Objective To establish and apply a Functional Observation Battery (FOB) test technique for mice to evaluate the central nervous system (CNS) function of drugs, providing a scientific basis for the safety pharmacology assessments. Methods Twenty quarantine-qualified ICR mice (10 males and 10 females) were divided into two experimental groups using stratified randomization based on gender and body weight: the vehicle control group (single intragastric administered 0.9% sodium chloride injection) and the chlorpromazine hydrochloride group (administered 25 mg/kg chlorpromazine hydrochloride solution via single oral gavage). The FOB tests were conducted once for each group of animals before dosing and at 1, 6, and 24 hours post-dosing. The tests included cage observations, open-field observations, handling observations, manipulative observations, and special observations. A total of 64 parameters across four major dimensions were evaluated: autonomic regulation, motor control and reflexes, emotional and behavioral responses, and central integrative functions. Quantitative scoring was performed to investigate drug effects on mouse CNS function. Results Compared with the vehicle control group, significant changes were observed in all four dimensions of the observation indicators in the chlorpromazine hydrochloride group from 1 h to 6 h after administration. The animals essentially recovered by 24 hours post-dosing. Conclusion The established d FOB test technique for mice can serve as an effective tool for the safety pharmacology evaluation of CNS function.