热环境中大鼠脑、肺损伤与米帕林的保护作用

背景高温环境对生物体造成明显损伤,深入研究热环境损伤的机制、提高机体耐热损伤的能力,可为抗热环境药物研究提供参考.目的观察预先使用米帕林,对热环境中大鼠损伤的作用,探讨急性热环境致机体脑、肺损伤作用和可能的保护措施.设计完全随机设计,对照实验研究.地点和材料地点为军事医学科学院研究所.材料为二级Wistar大鼠,雄性,体质量160～200g,由军事医学科学院实验动物中心提供,饲喂专用,饮用自来水.方法将大鼠随机分组,根据体质量灌胃给予不同剂量的米帕林,对照组给予相当体积的生理盐水,1h后进入41℃热环境.主要观察指标检测大鼠体温变化和死亡时间,分析药物剂量与体温变化、存活时间的关系.对死亡大鼠进行主要脏器的病理分析,寻找热环境对机体损伤的主要靶器官.结果41℃热环境明显影响大鼠的代谢和存活,进入热环境的大鼠体温经过短暂维持后迅速上升,大约在38min后死亡,死亡大鼠解剖发现肺明显出血和脑水肿,病理切片观察发现肺细胞和大脑神经元死亡明显;预先灌胃给予4.5～18.0mg/kg米帕林能够明显减缓大鼠在热环境下体温升高的速率,增加大鼠在热环境中的存活时间.9.0mg/kg剂量组体温上升速率减缓20%左右,存活时间延长超过50%.9.0 mg/kg剂量组大鼠在进入热环境38min左右处死后,解剖发现轻微肺出血和脑水肿,损伤明显轻于对照组.结论米帕林灌胃能够增强大鼠抗热致死的能力,具有保护热环境损伤的作用.

Protective role of mepacrine in cerebral and lung injuries of rats due to heat exposure

BACKGROUND: Heat cxposure may result in apparent injury in organism. Therefore, extensive research on the mechanism of thermal injury and thermotolerant capability will provide reference for exploring pharmacotherapy for injury due to heat exposure.OBJECTIVE: To observe the effectof mepacrine pretreatment on thermal injury in rat models so as to find out the mechanism of thermal injury due to acute heat exposure in lung and brain as well as possible protective method.DESIGN: Copmpletely randomized controlled trial SETTING and MATERIALS: The experiment was completed in the Institute of Basic Medicine, Military Medical Science Academy. Ⅱ class Wistar male rats, weighing 160-200 g, were provided by the Experimental Animal Center of Military Medical Science Academy, and raised with special feed and running water.METHODS: Rats were randomly divided into mepacrine group and control group, receiving mepacrine of different dosages by gastric lavage according to their weight or receiving saline of the same volume and one hour later they were put into heat environment of 41℃.MAIN OUTCOME MEASURES: The changes of body temperature and death time of the rats were elicited to analyze the correlation of medical dosage with the body temperature changes and survival time. Meanwhile, pathological changes were also investigated in major organs of dead rat so as to find out main target organs susceptible to heat exposure.RESULTS: Heat exposure of 41 ℃ obviously affected the metabolism and survival of the rats. After entering into the heat environment, rat maintained its temperature for a short time before rapidly increased to fatal degree 38 minutes later. Autopsy revealed apparent lung hemorrhage and cerebral edema with pathological manifestations including obvious lung cells death and cerebral neuronal death. Pretreatment with mepacrine of 4. 5-18.0 mg/kg by gastric lavage would distinctly reduce its temperature-increasing rate and prolong survival time of rat under heat circumstance. Rats pretreated with mepacrain of 9.0 mg/kg showed reduced temperature-increasing rate about 20% and prolonged survival time over 50%, accompanied by attenuated lung hemorrhage and cerebral edema, and the injuries were obviously better than those in the control group.CONCLUSION: Mepacrine can enhance thermotolerant capability for lethal heat exposure by gastric lavage, and then play an important protective role.