摘要
目的应用全身体积描记法观察药物对大鼠呼吸指标的影响,对动物肺功能检测系统进行性能验证,为该技术用于药物安全药理学评价提供依据。方法 SD大鼠30只,雌雄各半,分为溶媒对照组、巴氯芬(30 mg/kg)组、茶碱(30 mg/kg)组,溶媒对照组给予等体积的0.5%羧甲基纤维素钠溶液。实验时将动物放入体积描记箱中,动物肺功能检测系统连续获取给药前至少60 min及给药后6 h内的数据,药后24 h至少连续采集60 min的数据,将每只动物给药前、给药后1、2、4、6、24 h均选取连续平稳的30个呼吸波,检测潮气量(TV)、每分钟通气量(MV)、呼吸频率(F)。结果与溶媒对照组比较,巴氯芬组TV在给药后1、2、4、6、24 h显著增大(P<0.05),呈先上升后下降趋势;F在药后2、4、6 h显著减慢(P<0.05),呈先下降后上升趋势。大鼠给予30 mg/kg的茶碱后呼吸急促,药后1、2、4 h F明显加快、MV显著增加,均呈先上升后下降趋势,与溶媒对照组比较,药后1、2 h出现统计学差异(P<0.05)。结论 SD大鼠给予巴氯芬和茶碱后呼吸指标具有良好时间-反应趋势,可作为阳性药用于仪器的性能验证;肺功能检测系统能够准确记录清醒无束缚大鼠呼吸指标的变化情况,可用于呼吸系统安全药理学研究。
Objective To research the performance qualification of pulmonary function test system with whole-body plethysmography to observe the effect of drugs on rats, and to provide a basis for the future application of this technique for drug safety evaluation. Methods Totally 30 Sprague-Dawley rats were used in this study, 15 males and 15 females. The rats were divided into three groups： solvent control group, baclofen group, and theophylline group. The baclofen and theophylline group received a single dose of 30 mg/kg baclofen or theophylline, and the control group was given an equal volume of 0.5% carboxymethylcellulose sodium solution. In the experiment, rats were placed in a plethysmograph box. The animal lung function test system obtained data at least 60 min before and 6 h after administration. At least 60 min data were collected at least 24 h after administration, and 30 continuous and stable respiratory waves were selected for each animal at 1, 2, 4, 6, and 24 h after administration, and the tidal volume（TV）, minute ventilation（MV）, and respiratory rate（F） were detected. Results Compared with solvent control group, TV of the baclofen group increased significantly at 1, 2, 4, 6, and 24 h after administration（P〈0.05）, rising first and then descending; And F decreased at 2, 4, and 6 h after administration, descending first and then rising. F and MV of the theophylline group increased significantly at 1, 2 h after administration（P〈0.05）, rising first and then descending. Conclusion Based on the good time-response curve, baclofen and theophylline could be used as positive drugs in respiratory safety assessment, for its sensitive and good performance in SD rats. Respiratory signals could be acquired for 6 h continuously in conscious and unrestrained rats accurately with pulmonary function test system, and the system can be used for drug safety pharmacological research of respiratory system.
作者
刘艳菊
周博宇
钟飞
兰天龙
葛鹏
徐德璐
胡雷
LIU Yanju1, 2, ZHOU Boyu1, ZHONG Fei1, LAN Tianlong1, GE Peng1, XU Delu1, HU lei1, 2(1. Tianjin Institute of Pharmaceutical Research New Drug Evaluation Co. Ltd, Tianjin 300301, China ;2. Tianjin Engineering Research Center of Drug Preclinical Assessment Technology, Tianjin 300301, China)
出处
《药物评价研究》
CAS
2018年第8期1391-1394,共4页
Drug Evaluation Research
基金
国家科技重大新药创制项目(2015ZX09501004)
天津市科技计划项目(16PTGCCX00090)
关键词
全身体积描记法
巴氯芬
茶碱
清醒大鼠
呼吸系统
性能验证
潮气量
每分钟通气量
呼吸频率
whole-body plethysmography
baclofen
theophylline
conscious rats
respiratory system
performance qualification
tidal volume
minute ventilation
respiratory rate
