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Effect of chronic intermittent hypoxia on the expression of Nip3, cell apoptosis, β-amyloid protein deposit in mice brain cortex

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Chinese Medical Journal 2009年第1期122卷 68-73页

作者： ZENG Yi-ming CAI Kai-jin CHEN Xiao-yong WU Min-xia LIN Xi Department of Pulmonary Medicine the Second Affiliated Hospital of Fujian Medical University Quanzhou Fujian 362000 China Institute of Sleep and Breath Disorders Research Fujian Medical University Quanzhou Fujian 362000 China Department of Electronic Microscope Fujian Medical University Fuzhou Fujian 350000 China

Background Chronic intermittent hypoxia （CIH） is the most important pathophysiologic feature of sleep apnea syndrome （SAS）. To explore the relationship between SAS and dementia, the effects of CIH on the expression of Nip3, neuron apoptosis and β-amyloid protein deposit in the brain cortex of the frontal lobe of mice were evaluated in this study.Methods Thirty male ICRmice＇were divided into four groups： control group （A, n=-10, sham hypoxia/reoxygenation）, 2 weeks CIH group （B, n=5）, 4 weeks CIH group （C, n=-5）, and 8 weeks CIH group （D, n=10）. The ICR mice were placed in a chamber and exposed to intermittent hypoxia （oxygen concentration changed periodically from （21.72±0.55）% to （6.84±0.47）% every two minutes, eight hours per day）. Neuron apoptosis of the cortex of the frontal lobe was detected by means of terminal deoxy-nucleotidyl transferase-mediated in situ end labeling （TUNEL）. Immunohistochemical staining was performed for measuring expression of Nip3 and β-amyloid protein. The ultrastructure of neurons was observed under a transmission electron microscope.Results TUNEL positive neurons in each square millimeter in the cortex of the frontal lobe were categorized by median or Riinto group A （1, 5.5）, group B （133, 13）, group C （252, 21）, and group D （318, 24）. There were significant differences among the above four groups （P=0.000）. The significance test was performed between the control group and each CIH group respectively： group A and B （P 〉0.05）; group A and C （P 〈0.01）; and group A and D （P 〈0.005）. The number of apoptotic neurons kept increasing in the ICR mice under CIH condition, and reached the peak in the group D, but there was no significant difference between groups B and C, between groups B and D, and between groups C and D. Nip3 positive neurons in each square millimeter in the cortex of the frontal lobe in each group were calculated by median or Ri as follows： group A （2, 5.5）, group B （117, 13）, group C （227, 26.2）, and group D（479, 21.4）.

关键词： chronic intermittent hypoxia sleep apnea brain Nip3 apoptosis β-amyloidprotein

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