全身体积描记法在大鼠呼吸系统试验中的应用
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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.
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.
引文
[1]CFDA.药物安全药理学研究技术指导原则[EB/OL].(2014-05-13)[2018-04-06].http://www.cde.org.cn/zdyz.do?method=large Page&id=187.
[2]潘水珍,张利棕,潘永明,等.生理遥测和全体积描记法联用观测清醒大鼠昼夜节律变化及其在多索茶碱安全药理学中的应用[J].中国实验动物学报,2017,25(4):439.
[3]张颖丽,王超,王三龙,等.非束缚清醒大鼠呼吸功能测量系统3Q验证[A].//张颖丽.第四届药物毒理学年会论文集[C].昆明:中国毒理学.2014.
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[5]孙晓红,张宪成,黄春倩,等.清醒大鼠肺功能检测系统在全氟异丁烯吸入毒理研究中的应用[J].国际药学研究杂志,2011,38(6):446.
[6]王三龙,沈连忠,齐卫红,等.安全药理遥测系统进行3Q验证的关注点[J].中国药学杂志,2010,45(10):798.
[7]谢瑞满.巴氯芬临床应用研究进展[J].世界临床药物,2006,27(3):149-150.
[8]汪萌芽,朱蓉.解痉药巴氯芬研究进展[J].中国药理学通报,1992,8(5):335.
[9]Bowery N G,Hill D R,Hudson A L,et al.Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor[J].Nature,1980,283(5742):92-94.
[10]徐永健.吸呼肌疲劳治疗的研究近况[J].临床内科杂志,1991,8(5):10.
[11]黄爱霞,郑则广.茶碱缓释片联合噻托溴铵干粉治疗稳定期慢性阻塞性肺疾病的临床研究[J].现代药物与临床,2014,29(6):623-626.
[12]孙长虹,张长群,张占纺,等.沙美特罗替卡松粉吸入剂联合异丙托溴铵喷雾剂治疗慢性阻塞性肺疾病稳定期疗效评价[J].疑难病杂志,2011,10(7):538-539.
[13]黄怀焕,林俊锋,伍胜孟.多索茶碱与氨茶碱治疗老年患者支气管哮喘急性发作的疗效及对肺功能的影响[J].中国现代医学杂志,2015,25(32):101-104.
[2]潘水珍,张利棕,潘永明,等.生理遥测和全体积描记法联用观测清醒大鼠昼夜节律变化及其在多索茶碱安全药理学中的应用[J].中国实验动物学报,2017,25(4):439.
[3]张颖丽,王超,王三龙,等.非束缚清醒大鼠呼吸功能测量系统3Q验证[A].//张颖丽.第四届药物毒理学年会论文集[C].昆明:中国毒理学.2014.
[4]方贤磊,李杨,聂李亚,等.肺功能分析在放射性肺损伤防治药物药效评价中的作用[J].军事医学,2015,39(7):519-522.
[5]孙晓红,张宪成,黄春倩,等.清醒大鼠肺功能检测系统在全氟异丁烯吸入毒理研究中的应用[J].国际药学研究杂志,2011,38(6):446.
[6]王三龙,沈连忠,齐卫红,等.安全药理遥测系统进行3Q验证的关注点[J].中国药学杂志,2010,45(10):798.
[7]谢瑞满.巴氯芬临床应用研究进展[J].世界临床药物,2006,27(3):149-150.
[8]汪萌芽,朱蓉.解痉药巴氯芬研究进展[J].中国药理学通报,1992,8(5):335.
[9]Bowery N G,Hill D R,Hudson A L,et al.Baclofen decreases neurotransmitter release in the mammalian CNS by an action at a novel GABA receptor[J].Nature,1980,283(5742):92-94.
[10]徐永健.吸呼肌疲劳治疗的研究近况[J].临床内科杂志,1991,8(5):10.
[11]黄爱霞,郑则广.茶碱缓释片联合噻托溴铵干粉治疗稳定期慢性阻塞性肺疾病的临床研究[J].现代药物与临床,2014,29(6):623-626.
[12]孙长虹,张长群,张占纺,等.沙美特罗替卡松粉吸入剂联合异丙托溴铵喷雾剂治疗慢性阻塞性肺疾病稳定期疗效评价[J].疑难病杂志,2011,10(7):538-539.
[13]黄怀焕,林俊锋,伍胜孟.多索茶碱与氨茶碱治疗老年患者支气管哮喘急性发作的疗效及对肺功能的影响[J].中国现代医学杂志,2015,25(32):101-104.