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2018应用动物体温维持仪与仿真热气候动物舱建立大鼠经典型热射病的建

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发表于 2018-8-18 21:41:06 | 显示全部楼层 |阅读模式
  作者单位:510515 广州,南方医科大学附属武汉临床学院(李慧敏、陈芳、唐忠志);广州军区武汉总医院急诊科(陈晓娟、付炜、唐忠志)
  通信作者:唐忠志,Email:zhzhtang@163.com
  【摘要】目的比较应用动物体温维持仪与仿真热气候动物舱建立的大鼠经典型热射病(CHS)模型的异同。方法雄性SPF级Wistar大鼠24只,随机(随机数字法)分为室温对照(C-C)组、高温对照(HS-C)组、高温麻醉(HS-A)组。HS-C和HS-A 组大鼠分别使用仿真热气候动物舱和动物体温维持仪行35 ℃热暴露,监测各组大鼠动脉收缩压(SBP)、核心体温(Tc)变化,记录发病时间,比较两组大鼠白细胞(WBC)计数、C反应蛋白(CRP)、肿瘤坏死因子-(TNF-)、白介素-1(IL-1)等炎症指标变化及大脑、肺、肝、小肠、肾等主要器官病理改变。结果HS-A组大鼠发病时间比HS-C组明显缩短[(40.0  4.3) min vs.(110.1  5.3)min,P0.01],发病时SBP及Tc比HS-C组低(159.1  5.91) mmHg vs.(174.54  5.77) mmHg(1 mmHg=0.133 kPa),P 0.01;(43.5  0.4) ℃vs.(44.4  0.2) ℃,P 0.01)。建模后两组大鼠WBC、CRP、TNF-、IL-1水平较C-C组均显著升高(P0.01),且HS-A组炎性因子水平比HS-C组低(P0.01),但WBC计数差异无统计学意义(P0.05);两组大鼠大脑、肺、肝、小肠、肾等主要器官病理无明显改变。结论应用动物体温维持仪建立大鼠CHS模型与仿真热气候动物舱法差异无统计学意义,并且能够明显缩短建模时间、节约成本,是一种简易、可靠而又经济的模型建立方法,可以替代仿真热气候动物舱法。
  【关键词】】热射病;动物模型;大鼠动物;体温维持仪;仿真热气候动物舱
  Comparison between animal temperature controller and artificial climate chamber employed for the establishment of classical heat
  Li Huimin, Chen Xiaojuan, Chen Fang, Fu Wei, Tang Zhongzhi. Wuhan Clinical Institute Affiliated to Southern Medical University, Guangzhou 510515, China
  Corresponding author: Tang Zhongzhi, Email:zhzhtang@163.com
  【Abstract】ObjectiveTo investigate the differences between animal temperature controller (ATC) and artificial climate chamber (ACC) used for the establishment of classical heat stroke (CHS) rat model. MethodsTwenty-four male specific pathogen-free Wistar rats were randomly(random number) and equally assigned to three groups, namely room temperature control (C-C) group,heat stroke under conscious state (HS-C) group, and heat stroke under anesthesia (HS-A) group. Rats of HS-C or HS-A group were placed into ACC or ATC, then exposed to 35 ℃ heat stress. The systolic blood pressure (SBP) and core body temperature (Tc) were monitored. The time required for onset of HS was recorded. The white blood cell count (WBC) in peripheral blood and serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-) and interleukin-1 beta (IL-1) were measured. The histopathological changes of major organs were also confirmed by hematoxylin-eosin (HE) staining. ResultsThe onset time in HS-A group was significantly shorter than that in HS-C group [(40.0  4.3)min vs.(110.1  5.3)min,P0.01]. The SBP and Tc at this moment were lower in HS-A group[ (159.1  5.91) mmHg vs.(174.54  5.77)mmHg,P0.01;(43.5  0.4)℃ vs.(44.4  0.2)℃,P0.01]. The WBC, CRP, TNF- and IL-1 levels of these two HS groups were dramatically elevated compared with C-C group (P0.01). The inflammatory cytokines levels in HS-A group were significantly lower than those in HS-C group (P0.01), but there was no difference in WBC between them (P0.05). However, there was no obvious difference in histopathological change in major organ observed between HS-A and HS-C groups. ConclusionsIn comparison of these two methods, ATC is similar to ACC in respect of the establishment of CHS rat model. ATC is quicker in onset of HS, and more simplified and economical than ACC and could substitute ACC.
 【Key words】Heat stroke; Experiment animal model; Rat;Animal temperature controller;Artificial climate chamber
  热射病(heat stroke,HS) 是一种急性热致疾患,典型临床表现为高热(40 ℃) 、无汗和意识障碍sup[1]/sup,病死率高达10%~50%sup[2-4]/sup,即便幸存者也有约30%遗留永久性神经系统及肢体功能障碍sup[5]/sup。按发病原因不同分为经典型热射病(classical heat stroke, CHS)和劳力型热射病(exertional heat stroke, EHS)sup[1]/sup。随着全球气候变暖和城市热岛效应加剧,夏季极端气候不断出现,HS的发生率和病死率明显上升sup[6-9]/sup,已经成为严重威胁公共健康的疾病之一。目前HS的发病机制尚不清楚,而HS动物模型的建立对阐明其机制具有重要意义。传统的CHS动物模型建立方法是将大鼠置于仿真热气候动物舱内、模拟高温高湿环境促使其发病。然而仿真热气候动物舱设备价格昂贵、体积庞大,因而限制了其应用。而动物体温维持仪建模时间短、成本低、实验条件要求相对降低,具有广泛应用的潜在价值,但目前尚无两种方法对比的研究。因此,本研究旨在比较两种建模方法的异同,评估动物体温维持仪建模方法的应用价值。
  1材料与方法
  1.1主要仪器设备及试剂
  仿真热气候动物舱(南方医科大学公共卫生与热带医学学院提供),PowerLab数据采集分析系统(澳大利亚ADInstruments公司),SS-20-2型动物体温维持仪(安徽淮北正华生物仪器设
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