慢性缺氧/再氧合小鼠脑皮质Nip3表达及其与神经细胞凋亡的关系

The expression of Nip3 and its relationship with neuron apoptosis in the cerebral cortex of mice following chronic hypoxia/reoxygenation

目的研究慢性缺氧/再氧合对小鼠脑皮质Nip3的表达及神经细胞凋亡的影响,探索睡眠呼吸暂停综合征(SAS)脑损害的可能机制。方法自制慢性缺氧/再氧合小鼠模型:通过控制程序调控箱内氧浓度,使得每一间断性缺氧循环时间为2 min,氧浓度循环于(21.72±0.55)%与(6.84±0.47)%之间,每天缺氧/再氧合8 h。30只ICR小鼠随机分为4组:模拟对照组10只,缺氧/再氧合二周组及四周组各5只,缺氧/再氧合八周组10只。免疫组织化学方法检测小鼠额叶脑皮质Nip3的表达,TUNEL法检测脑神经细胞凋亡。结果与模拟对照组比较,缺氧/再氧合各组脑皮质Nip3的表达和凋亡神经细胞数均显著增加(P<0.05),八周组与四周组Nip3的表达和凋亡神经细胞数较二周组亦显著增加(P<0.05),八周组与四周组比较差异无统计学意义(P>0.05);脑皮质Nip3的表达与脑神经细胞凋亡之间存在正相关关系(r=0.901,P<0.05)。结论慢性缺氧/再氧合可增加脑Nip3的表达,引起皮质脑神经细胞凋亡,可能是其神经系统损害的机制之一。

Objective To evaluate the impact of chronic hypoxia/reoxygenation on the Nip3 expression and neuron apoptosis in the cerebral cortex of mice, and explore the possible mechanism of damage to the brain by sleep apnea syndrome （SAS）. Methods The establishment of mouse models of chronic hypoxia/reoxygenation： Male ICR mice were placed in a chamber, where the oxygen concentration changed periodically from （21.72 ±0.55）% to （6.84 ±0.47）% every 2 min, hypoxia/reoxygenation 8 h per day. The 30 male ICR mice were randomly divided into four groups： control group （n=10） and hypoxia/reoxygenation groups （n=20）, which consisted of hypoxia/reoxygenation 2-week group （n=5）, g-week group （n=5） and 8-week group （n=10）. Immunohistochemical techniques and terminal deoxy-nucleotidyl transferase-mediated dUTP-biotin nick end-labeling （TUNEL） assay were respectively used to detect the expression of Nip3 in the frontal lobe cortex of mice and neuron apoptosis. Results The expression of Nip3 and number ofapoptotic neural cells in the cerebral cortex of hypoxia/reoxygenation groups were all increased, compared with that of the control group （P〈0.05） and that in the 8-week and 4-week groups were also higher than that in the 2-week group （P〈0.05）; the comparison between the 8-week and 4-week groups had no statistical significance （P〉0.05）. The expression of Nip3 was positively correlated with neuron apoptosis in the cerebral cortex （r=0.901, P〈0.05）. Conclusion Chronic hypoxia/reoxygenation may enhance the expression of Nip3 in the cerebral cortex and initiate apoptosis of cortical neurons, and thus, it might be one of the mechanisms for the damage to the nervous system.