模拟高原缺氧不同时间对大鼠心肌线粒体功能的影响及其在习服—适应中的意义

EFFECTS OF HYPOXIA ON RAT HEART MITOCHONDRIAL FUNCTION AND THEIR SIGNIFICANCE IN ADAPTATION TO HYPOXIA OF HIGH ALTITUDE

目的：观察模拟高原缺氧不同时间对心肌线粒体的影响，探讨模拟高原缺氧对机体影响的细胞机制以及线粒体功能改变在机体对缺氧习服—适应中的意义，为高原缺氧性疾病的防治提供理论基础。方法：观察急性连续缺氧（模拟５ ０００ｍ 高原）３、１２、３６ 和７２ 小时以及慢性间断缺氧１４、２８ 和４２天对大鼠心肌线粒体的影响。测定了线粒体呼吸控制率、琥珀酸脱氢酶及细胞色素氧化酶活性和线粒体丙二醛含量。结果：各时间点的线粒体呼吸控制率比对照组都显著降低，急性缺氧的下降程度较慢性组为甚，其中急性缺氧３ 小时组抑制程度最显著。细胞色素氧化酶活性在急性缺氧３ 小时末显著降低，随后有所回升，而慢性缺氧则使细胞色素氧化酶活性升高。琥珀酸脱氢酶活性在急性缺氧组升高。线粒体丙二醛含量在急性与慢性缺氧各时间点均显著升高，其中以３ 小时组的丙二醛值为最高。结论：急性缺氧、尤其是在最初３ 小时心肌线粒体呼吸功能受抑制较严重，线粒体细胞色素氧化酶和琥珀酸脱氢酶活性升高可能有一定的代偿适应意义。

To clarify the effect of hypoxia on mitochondrial function of Wistar rat and their significance in adaptation to hypoxia of simulated high altitude. Methods:Rats were divided into 3 groups :(1)The normoxic control;(2)Acute hypoxic group in which rats were exposed to continuous hypoxia,at simulated altitude of 5 000m,for 3,12,36,and 72 hours respectively;(3)Chronic hypoxic group in which rats were subjected to intermittent hypoxia,at simulated altitude of 5 000m 8hrs/day,for 14,28,and 42 days respectively.Glutamate and malate-stimulated respiratory rate,lipid peroxide level,succinate dehydrogenase and cytochrome oxidase activities of mitochondria isolated from myocardial tissue were determined.Results:Significant decreases in respiratory capacity in 3hr-hypoxia rats were observed.In the chronic hypoxic groups.mitochondria respiratory capacity was also decreased,but not as significant as in the acute gruop.Cytochrome oxidase activities increased in most hypoxic groups,but a significant decrease in the activity of the cytochrome oxidase was observed in 3hr group,The succinate dehydrogenase activity increased in acute hypoxic groups.The lipid peroxide level of mitochondria increased in all hypoxic groups,especially in 3hr-hypoxia rats.Conclusions:The results indicate that acute and chronic hypoxia can depress the respiratory capacity of the myocardial mitochandria,especially marked at the early stage(end of the third hour).The increase of mitochondrial cytochrome oxidase and succinate dehydrogenase activities may play a role in adaptation to hypoxia of high altitude.$$$$