模拟高原缺氧环境对大鼠心、脑组织损伤的研究

Study on myocardium and brain damage in rats by simulating high altitude

目的采用大型低压低氧动物实验舱模拟海拔6 000m低氧低温环境,探讨不同暴露时间对大鼠心、脑组织损伤的程度,为建立大鼠急性高原病模型及其相关机制研究奠定基础。方法 32只健康雄性Wistar大鼠随机分为正常对照组及低氧低温1、3、5d组,每组8只。正常对照组大鼠饲养于当地海拔高度(1 500m),不予处理;其余3组根据不同暴露时间置于低压氧舱模拟海拔6 000m高原进行低氧低温处理。HE染色观察心、脑组织病理改变,并检测相关生化指标的变化,评价不同暴露时间对大鼠心、脑组织的损伤情况。结果 HE染色结果显示,低氧低温引起大鼠心、脑组织不同程度的损伤,其中心肌组织在上述实验条件下随暴露时间的延长损伤加重,而脑组织在3d时损伤最为严重;与正常对照组相比,各组心肌组织丙二醛(malondialdehyde,MDA)含量、乳酸(lactid acid,LD)含量随时间延长而明显增加(P<0.05或P<0.01),还原型谷胱甘肽(reduced glutathione,GSH)含量、总超氧化物歧化酶(total superoxide dismutase,T-SOD)、Na+K+-ATPase活力随时间延长而明显降低(P<0.05或P<0.01);脑组织MDA含量在1d及3d时有显著升高(P<0.05或P<0.01),LD含量随时间延长而明显升高(P<0.05),GSH含量、T-SOD及Na+K+-ATP酶活力仅在3d时降低最为明显(P<0.05)。结论模拟海拔6 000m高原环境对大鼠心、脑组织造成明显损伤,且损伤程度与暴露于低氧低温的时间有关,机体抗氧化能力降低、自由基增加和能量代谢障碍是导致其损伤的重要因素。

Objective To investigate the effect of hypoxia with cold on the heart and brain damage in rats by simulating6 000 mhigh altitude at different exposure time,established a rat model of acute mountain sickness for the related mechanism studies.Methods 32 healthy male Wistar rats were randomly divided into normal control group,hypoxia with cold 1 d,3 d and 5 dgroup,8 rats in each group.The normal control group was kept in the plain environment（1 500 m）without any treatment.The other three groups were placed in large hypobaric hypoxia chamber to simulate 6 000 maltitude with different exposed times.HE staining was used to observe the pathological changes of heart and brain tissue.The changes of biochemical indexes were measured to evaluate the damage of heart and brain tissue at different hypoxia times.Results HE staining showed that hypoxia with cold induced rat heart and brain damage with different degrees.The myocardial tissue damage was increased with exposure time.The most serious brain damage happened in day 3.Compared with the normal control group,the content of MDA and LD in the myocardial tissue of hypoxia rats were significantly increased（P〈0.05 or P〈0.01）with prolonged time,while the contents of GSH,T-SOD and the activity of Na^＋K^＋-ATPase were reduced（P〈0.05 or P〈0.01）.The content of MDA in brain tissue was significantly increased at day 1 and day 3（P〈0.05 or P〈0.01）.LD content was significantly increased（P〈0.05）with time.The content of GSH,the activity of T-SOD and Na^＋K^＋-ATPase were significantly reduced in day 3（P〈0.05）.Conclusion Simulating an altitude of 6 000 mcaused obvious damage on the heart and brain tissues of rats.The degree of damage was related to the exposure time to hypoxia with cold.The decrease of body′s antioxidant capacity,the increase of free radicals and energy metabolism disorders are important factors leading to heart and brain injury.