慢性低氧高二氧化碳对小鼠大脑线粒体功能的影响

Dysfunction of the mitochondria in the cerebrum of mice induced by chronic hypoxic hypercapnia

目的:探讨慢性低氧高二氧化碳对小鼠大脑线粒体功能的影响。方法:雄性C57BL/6小鼠30只,随机分成2组:A组(低氧高二氧化碳组15只)和B组(正常对照组15只)。A组饲养于氧舱中,舱内氧浓度为9%～11%,二氧化碳浓度为5%～6%,每天8h～每周6d,共4周,其余时间与B组一样,生活于正常环境。测量脑组织ATP,ADP,AMP的浓度;线粒体膜电位、COXⅠ和Ⅲ活性。结果:低氧高二氧化碳组小鼠脑组织ATP,AMP浓度显著低于正常对照组(P<0.01),线粒体形态明显改变,脑线粒体膜电位低下、COXⅠ和Ⅲ活性受到抑制(P<0.01),脑组织SOD、GSH活性降低(P<0.01)。结论:慢性低氧高二氧化碳可导致小鼠大脑线粒体功能明显异常,其机制可能与氧化应激反应有关。

Objective： To explore the influence of chronic hypoxic hypercapnia on the mitochondria in the cerebrum of the mice.Methods： Thirty male C57BL/6 mice were randomly divided into two groups： the hypoxic hypercapnia 4-week experiment group （A group） and normal control group （B group）.The experiment group was exposed to an atmosphere containing 9%～11% O2 and 5%～6% CO2 8 hours a day,6 days a week for 4 weeks.The rest time A group lived in the room as B group did.The concentration of ATP,ADP and AMP was measured by HPLC.The changes of the ultramicrostructures in the mitochondria of the cerebrum were observed under the transmission electron microscope.The membrane potential of the mitochondria was observed by the confocal and the intensity was measured by spectrophotofluorometry.The activity of the COX Ⅰ or COX Ⅲ in the mitochondria and the SOD or GSH in the tissue of the cerebrum were measured by spectrophotofluorometry,respectively.Results： Compared with the normal control group,the concentration of the ATP and AMP of mice was lower obviously （P0.01）.the ultramicrostructures were abnormal and the density of the membrane potential decreased of the mitochondria,the activity of the COX Ⅰ or COX Ⅲ in the mitochondria of the cerebrum and the SOD or GSH in the cerebrum tiusse was also decreased significantly respectively （P0.01）.Conclusion： Under the condition of exposue to chronic hypoxic hypercapnia,the dysfunction of the mitochondria in the mice’s cerebrum may occur.Its mechanism may be related to the free radical.