Effect Of Chronic Hypoxia/Reoxygenation On The Expression Of Nip3, Apoptosis And β-Amyloid Protein Deposit In Mice Brain

Objective To evaluate the effect of chronic hypoxia/reoxygenation on the expression of Nip3, Apoptosis andβ-Amyloid Protein deposit in mice brain. Methods To establish the animal model of chronic hypoxia/ reoxygenation: male ICR mice were placed in a chamber, where oxygen concentration changed periodically from (21.72±0.55)% to (6.84±0.47)% every two minutes, eight hours per day. Thirty male ICR mice were divided into four groups: ten for control group (sham hypoxia/ reoxygenation), twenty for hypoxia/ reoxygenation groups (each five for 2–week group and 4-week group, ten for 8-week group). Apoptosis was determined by terminal deoxy-nucleotidyl transferase-mediated in situ end labeling (TUNEL). Immunohistochemistry was used to examine the expression of Nip3 andβ-Amyloid Protein. Ultrastructure of neurons of mice brain cortex was observed by transmission electron microscope. Results The nerve cells apoptosis and expression of Nip3 in mice brain were mostly distributed in the cortex. The number of nerve cells apoptosis in mice brain of all hypoxia/reoxygenation groups significantly increased compared with that of the control group (P<0.01), the nerve cells apoptosis in mice brain of the 8-week group and the 4-week group also significantly increased compared with that of the 2 weeks group(P<0.01), the number of nerve cells apoptosis in mice brain keep increasing after hypoxia/reoxygenation, and reach the peak at eighth week, but there was no significant difference between the 8-week group and the 4-week group(P>0.05). The number of Nip3-positive cells in mice brain of all hypoxia/reoxygenation groups significantly increased compared with that of the control group (P<0.01), Nip3 of the 8-week group and the 4-week group also significantly increased compared with that of the 2-week group(P<0.01), the number of Nip3-positive cells in mice brain keep increasing after hypoxia/reoxygenation, and reach the peak at fourth week, decreased at eighth week, but there was no significant difference between the 8-week group and the 4-week group(P>0.05). The expression of Nip3 was positively correlated with nerve cells apoptosis in mice brain(r =0.901,P<0.05). The expression ofβ-Amyloid Protein in brain of mice was negative in all hypoxia/reoxygenation groups and control group. Ultrastructure: more nerve cells apoptosis, deposited lipofuscins, swelling chondriosomes and neural sheath degeneration were observed in the 8-week group. Conclusion The results suggest that chronic hypoxia/ reoxygenation may up-regulate the expression of Nip3, cause the brain damage, including nerve cells apoptosis, swelling chondriosomes,deposited lipofuscins and neural sheath degeneration.