目的 观察世居平原男性青年高原习服各时程淋巴细胞线粒体能量代谢、线粒体DNA(mtDNA)拷贝数及其氧化损伤的动态变化规律。方法 27名世居平原武警新兵急进高原,分别在移居高原3、7、90 d检测淋巴细胞线粒体膜电位、mtDNA中8-oxodG含量、mtDNA拷贝数和PGC-1α蛋白表达。结果 与平原阶段比较,移居高原3 d和7 d,膜电位显著降低(P<0.05),8-oxodG含量,mtDNA拷贝数和PGC-1α表达显著升高(P<0.05);移居高原90 d,mtDNA拷贝数和PGC-1α表达显著降低(P<0.05)。移居高原90 d与移居高原7 d比较,膜电位显著升高(P<0.05),8-oxodG含量,mtDNA拷贝数和PGC-1α表达显著降低(P<0.05)。结论 高原习服初期淋巴细胞能量重构主要依赖于线粒体数量增加,而在高原习服后期主要依赖于单个线粒体健康程度及能量代谢水平提高。
Abstract
Objective To study the changes in mitochondrial bioenergetics, mitochondrial DNA (mtDNA) and oxidative damage in leukocytes during acclimatization to highland hypoxia. Methods Twenty-seven lowlanders quickly entered plateau. Leukocyte mitochondrial membrane potential, 8-oxodG in mtDNA, mtDNA copies and PGC-1α protein expression were measured in plain and plateau at 3 d,7 d,90 d after entry. Results As compared with plain group, membrane potential was significantly decreased (P<0.05); 8-oxodG amounts, mtDNA copies and PGC-1α expression were markedly increased at 3 d and 7 d (P<0.05). And at 90 d, mtDNA copies and PGC-1α expression were significantly decreased (P<0.05). As compared with 7 d group, membrane potential was significantly increased (P<0.05); 8-oxodG amounts, mtDNA copies and PGC-1α expression were markedly decreased at 90 d (P<0.05). Conclusions In the early phase of acclimatization to highland, leukocyte bioenergetics remodeling mainly depends on increased mitochondrial content. In the later phase of acclimatization to highland, leukocyte bioenergetics remodeling mainly depends on elevated level of single mitochondrial health and energy metabolism.
关键词
高原习服 /
淋巴细胞 /
线粒体DNA /
拷贝数 /
氧化损伤
Key words
acclimatization to high-altitude /
leukocytes /
mitochondrial DNA /
copy number /
oxidative stress
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参考文献
[1] 佟长青,薄 海,李海英,等. 急进高原和高原训练对武警新兵血氧血压综合参数的影响[J]. 职业与健康, 2011, 27(17): 1921-1923.
[2] Faoro V, Fink B, Taudorf S, et al. Acute in vitro hypoxia and high-altitude (4,559 m) exposure decreases leukocyte oxygen consumption.[J]. Am J Physiol Regul Integr Comp Physiol, 2011, 300(1): 32-39.
[3] 罗勇军,刘福玉,陈 丽,等. 高原习服适应中白细胞线粒体DNA拷贝数的变化规律[J]. 第三军医大学学报,2011, 33(4): 359-375.
[4] Mariggio M A, Falone S, Morabito C, et al. Peripheral blood lymphocytes: a model for monitoring physiological adaptation to high altitude.[J]. High Alt Med Biol, 2010, 11(4): 333-342.
[5] 彭 朋,薄 海,王大宁,等.连续3 d大负荷军事训练对武警战士淋巴细胞亚群的影响[J]. 武警医学, 2012, 23(11): 941-943.
[6] 薄 海,王义和,李海英,等. 耐力训练抑制急性低氧时骨骼肌线粒体生物能学变化:ROS和UCP3的作用[J]. 生理学报, 2008, 60(6): 767-776.
[7] 刁秋霞,薄 海,秦永生,等. 军事训练致肌肉损伤的发生机制及其生物化学标志物[J]. 武警医学, 2013, 24(6): 523-525.
[8] Ballinger S W, Patterson C, Yan C N, et al. Hydrogen peroxide- and peroxynitrite-induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells.[J]. Circ Res, 2000, 86(9): 960-966.
[9] Ferro E, Visalli G, Civa R, et al. Oxidative damage and genotoxicity biomarkers in transfused and untransfused thalassemic subjects[J]. Free Radic Biol Med, 2012, 53(10): 1829-1837.
[10] Colleoni F, Padmanabhan N, Yung H W, et al. Suppression of mitochondrial electron transport chain function in the hypoxic human placenta: A role for miRNA-210 and protein synthesis inhibition[J]. PLoS One, 2013, 8(1): e55194.
[11] Gutsaeva D R, Carraway M S, Suliman H B, et al. Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism.[J]. J Neurosci, 2008, 28(9): 2015-2024.
[12] Levett D Z, Radford E J, Menassa D A, et al. Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest[J]. FASEB J, 2012, 26(4): 1431-1441.
[13] Gamboa J L, Andrade F H. Mitochondrial content and distribution changes specific to mouse diaphragm after chronic normobaric hypoxia.[J]. Am J Physiol Regul Integr Comp Physiol, 2010, 298(3): 575-583.
[14] Bo H, Zhang Y, Ji L L. Redefining the role of mitochondria in exercise: a dynamic remodeling.[J]. Ann N Y Acad Sci, 2010, 1201(1): 121-128.