摘要
本文旨在观察低氧复合运动对低氧状态下大鼠骨骼肌线粒体DNA(mtDNA)氧化损伤及线粒体8-氧鸟嘌呤DNA糖基化酶(OGG1)表达的影响,并探讨其可能机制。雄性Sprague-Dawley(SD)大鼠随机分为常氧对照组(NC)、常氧运动组(NT)、低氧对照组(HC)和低氧复合运动组(HT)。低氧干预为常压低氧帐篷,11.3%氧浓度持续暴露4周。运动干预为跑台训练(5o,15m/min),60 min/d,5 d/周,共4周。结果显示,HC组与NC组比较,线粒体复合体I、II、IV、ATP合成酶活性和膜电位显著降低(P<0.05或P<0.01),锰超氧化物歧化酶(MnSOD)、谷胱甘肽过氧化物酶(GPx)和OGG1活性显著降低(P<0.05或P<0.01),线粒体活性氧(ROS)生成速率和mtDNA中8-oxodG含量显著升高(P<0.01),SIRT3蛋白表达、骨骼肌和线粒体烟碱胺腺嘌呤二核苷酸氧化还原型比值([NAD+]/[NADH])显著降低(P<0.05或P<0.01)。HT组和HC组比较,线粒体复合体I、II、IV、ATP合成酶活性和膜电位显著升高(P<0.05或P<0.01),MnSOD、GPx、OGG1活性和线粒体OGG1蛋白表达显著升高(P<0.01),线粒体ROS生成速率和mtDNA中8-oxodG含量显著降低(P<0.01),SIRT3蛋白表达、骨骼肌和线粒体[NAD+]/[NADH]显著升高(P<0.05或P<0.01)。以上结果提示,低氧复合运动可上调线粒体OGG1和抗氧化酶,抑制低氧诱导的mtDNA氧化损伤,运动训练对[NAD+]/[NADH]和SIRT3的上调可能参与了对骨骼肌线粒体低氧耐受能力的增强调控。
This study was undertaken to investigate the effect of exercise training on mitochondrial DNA（mtDNA） oxidative damage and 8-oxoguanine DNA glycosylase-1（OGG1） expression in skeletal muscle of rats under continuous exposure to hypoxia. Male Sprague-Dawley rats were randomly divided into 4 groups（n = 8）： normoxia control group（NC）, normoxia training group（NT）, hypoxia control group（HC）, and hypoxia training group（HT）. The hypoxia-treated animals were housed in normobaric hypoxic tent containing 11.3% oxygen for consecutive 4 weeks. The exercise-trained animals were exercised on a motor-driven rodent treadmill at a speed of 15 m/min, 5% grade for 60 min/day, 5 days per week for 4 weeks. The results showed that, compared with NC group, hypoxia attenuated complex I, II, IV and ATP synthase activities of the electron transport chain, and the level of mitochondrial membrane potential in HC group（P〈0.05 or P〈0.01）. Moreover, hypoxia decreased mitochondrial OGG1, MnSOD, and GPx activities（P〈0.05 or P〈0.01）, whereas elevated reactive oxygen species（ROS） generation and the level of 8-oxo-deoxyguanosine（8-oxodG） in mtDNA（P〈0.01）. Furthermore, hypoxia attenuated muscle and mitochondrial [NAD＋]/ [NADH] ratio, and SIRT3 protein expression（P〈0.05 or P〈0.01）. Compared with HC group, exercise training in hypoxia elevated complex I, II, IV and ATP synthase activities, and the level of mitochondrial membrane potential in HT group（P〈0.05 or P〈0.01）. Moreover, exercise training in hypoxia increased MnSOD and GPx activities and mitochondrial OGG1 level（P〈0.01）, whereas decreased ROS generation and the level of 8-oxodG in mtDNA（P〈0.01）. Furthermore, exercise training in hypoxia increased muscle and mitochondrial [NAD＋]/[NADH] ratio, as well as SIRT3 protein expression（P〈0.05 or P〈0.01）. These findings suggest that exercise training in hypoxia can decrease hypoxia-induced mtDNA oxidative damage in the skeletal muscle through up-regulating exercise-induced mitochondrial OGG1 and antioxidant enzymes. Exercise training in hypoxia may improve hypoxia tolerance in skeletal muscle mitochondria via elevating [NAD＋]/[NADH] ratio and SIRT3 expression.
出处
《生理学报》
CAS
CSCD
北大核心
2014年第5期597-604,共8页
Acta Physiologica Sinica
基金
supported by the grants from the National Natural Science Foundation of China(No.31200894)
the Application Foundation and Cutting-edge Technology Research Project of Tianjin Municipality
China(No.12JCQNJC07900)
