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目的大量研究显示脑红蛋白(neuroglobin,NGB)对缺氧缺血性脑损伤具有保护作用。本研究探讨了SD大鼠暴露于高原低压低氧后NGB的表达情况,为阐明高原低氧性脑损伤的发生机制提供了新的思路。方法 70只雄性SD大鼠按体重随机分为两组,正常对照组(N=10,西宁,海拔2260米)和实验组(N=60,可可西里,海拔4600米),实验组是经西宁陆运至可可西里(海拔4600米)制作的急慢性高原缺氧模型组;依据高原暴露时间不同,将实验组又随机分为缺氧12 h组、24 h组、48 h组、72 h组、168 h组、720 h组(慢性组),每组10只。采用RT-PCR和Western blot检测高原低氧暴露不同时间脑皮质神经元中NGB mRNA和蛋白的表达含量。结果大鼠初入特高海拔地区后,Sa O2较对照组明显下降(P<0.01),适应一段时间后Sa O2开始回升,但168 h组和720 h组仍明显低于对照组(P<0.05);HR的变化则相反。与对照组相比,高原低压低氧暴露24 h(mRNA表达128.01±19.82;蛋白表达11.58±3.03)脑皮质神经元中NGB的表达出现首个高峰,此后逐渐下降,至168 h(mRNA表达72.52±16.02;蛋白表达5.99±1.70)恢复正常(P>0.05),而后有缓慢升高趋势,至720 h(mRNA表达99.38±21.26;蛋白表达8.50±2.98)后保持一个较高水平。结论急慢性高原低氧环境下,脑红蛋白表达的增高,增强了大鼠对高原低氧的耐受性,提示NGB表达变化可能是脑组织对脑缺氧的一种内源性神经保护反应,增加了脑组织的供氧,维持了神经元的正常功能。
Purpose A large number of studies have shown that neuroglobin (NGB) has a protective effect on hypoxic-ischemic brain damage. This study explored the expression of NGB after exposure to low altitude hypoxia in SD rats and provided a new idea for elucidating the pathogenesis of hypoxic brain injury at high altitude. Methods Seventy male Sprague-Dawley rats were randomly divided into two groups according to body weight: normal control group (N = 10, Xining, 2260 m above sea level) and experimental group (N = 60, Kekexili, 4600 m above sea level) To the Kekexili (4600 meters above sea level) made of acute and chronic plateau hypoxia model group; according to the different plateau exposure time, the experimental group were randomly divided into hypoxia 12 h group, 24 h group, 48 h group, 72 h group, 168 h Group, 720 h group (chronic group), 10 rats in each group. RT-PCR and Western blot were used to detect the expression of NGB mRNA and protein in cerebral cortical neurons at different time points after plateau exposure. Results Sa O2 decreased significantly (P <0.01) after initial admission into the extra-high altitude area. Sa O2 began to rise after a period of adaptation, but remained significantly lower at 168 h and 720 h (P < 0.05); HR changes on the contrary. Compared with the control group, NGB expression in cortical neurons reached the first peak at 24 h after hypoxia exposure (mRNA expression 128.01 ± 19.82; protein expression 11.58 ± 3.03), and then decreased gradually to 168 h (mRNA expression 72.52 ± 16.02; protein expression 5.99 ± 1.70) returned to normal (P> 0.05), and then increased slowly. After 720 h (mRNA expression was 99.38 ± 21.26; protein expression was 8.50 ± 2.98), a high level was maintained. Conclusion The elevated expression of neuroglobin under acute and chronic hypoxia may increase the tolerance of rats to altitude hypoxia, suggesting that the changes of NGB expression may be an endogenous neuroprotective effect of brain tissue on cerebral hypoxia , Increase the oxygen supply of brain tissue, maintain the normal function of neurons.