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

发布时间：2018-01-27 09:30

本文关键词： 遥测系统肺功能清醒大鼠安全药理学多索茶碱　出处：《中国实验动物学报》2017年04期 　论文类型：期刊论文

【摘要】：目的应用植入式生理信号遥测系统和全身体积描记法肺功能检测技术系统,观察清醒大鼠的昼夜节律变化,并用多索茶碱进行性能验证,为今后该技术系统用于药物安全药理学评价提供依据。方法 SD大鼠8只,雌雄各半,采用外科术将植入子植入大鼠腹腔建立遥测系统,并结合肺功能检测技术,在术后14 d观察清醒大鼠24 h的生理参数及昼夜节律的变化,包括心率(HR)、血压、心电图Q波到血压的舒张点的时间差(QA间期)、呼吸、活动、体温和肺功能等指标,分为正常对照组、多索茶碱40和80 mg/kg组(雾化吸入),观察给药后上述参数的变化情况。结果术后14 d清醒大鼠的生理指标具有明显的昼夜节律变化。与正常对照组比较,多索茶碱40mg/kg组大鼠HR、潮气量(TV)、每分钟通气量(MV)、50%呼气流量(EF50)、吸气流量峰值(PIF)和呼吸流量峰值(PEF)均明显增加(P0.01),呼吸频率、QA间期和增强呼气间歇(PENH)均明显降低(P0.05,P0.01),但对血压、活动和体温变化不明显;多索茶碱80 mg/kg组大鼠HR、血压、TV、MV、EF50、PIF和PEF均明显增加(P0.01),呼吸频率、QA间期和PENH均明显降低(P0.01),但对活动和体温变化不明显。结论本技术系统对大鼠的生理昼夜节律无明显影响,并可灵敏监测到心血管呼吸系统的相关变化,可用于清醒大鼠心血管呼吸系统安全药理学研究。
[Abstract]:Objective to observe the circadian rhythm of conscious rats with implantable physiological signal telemetry system and systemic pulmonary function test system, and to verify the performance of doxofylline. Methods eight Sprague-Dawley rats, half male and half female, were implanted into the abdominal cavity of rats by surgical technique to establish a telemetering system. The physiological parameters and circadian rhythm of conscious rats were observed on the 14th day after operation, including heart rate, HRT and blood pressure. The time difference between Q wave and diastolic point of blood pressure (QA), respiration, activity, body temperature and pulmonary function were divided into normal control group, doxofylline 40 and 80 mg/kg group (aerosol inhalation). Results the circadian rhythm of the physiological indexes of conscious rats was significantly changed 14 days after operation. Compared with the normal control group, the HR of rats in 40 mg / kg doxophylline group was higher than that in the control group. Tidal volume (TVV), 50% expiratory flow (EF50) per minute, peak inspiratory flow (PIFs) and peak respiratory flow (PEF) increased significantly (P 0.01). The frequency of respiration, QA interval and enhanced expiratory interval (PENH) were significantly decreased, but there were no significant changes in blood pressure, activity and body temperature. In Doxotheophylline 80 mg/kg group, the blood pressure and the blood pressure of TVB / EF50 / PIF and PEF increased significantly (P 0.01) and the respiratory frequency was significantly higher than that in the control group (P < 0.05). Both QA interval and PENH significantly decreased P0.01g, but had no significant effect on the activity and body temperature. Conclusion the system has no significant effect on the circadian rhythm of rats. It can be used in the pharmacological study of cardiovascular respiratory system safety in awake rats.
【作者单位】：浙江省医学科学院安全性评价研究中心;浙江中医药大学动物实验研究中心/比较医学研究所;
【基金】：浙江省公益性技术应用研究计划(2014C37012;2011C37076) 浙江中医药大学校级科技创新团队(XTD201301)
【分类号】：R965
【正文快照】： Corresponding author:SHOU Qi-yang.E-mail:sqy133@126.com临床前安全药理学试验主要研究药物在治疗或高于治疗剂量水平时,潜在的不期望出现的对生理机能的不良反应,其中中枢神经系统、心血管系统和呼吸系统是临床前安全药理学评价最主要的三大系统,即核心组合实验[1]。然而,

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