Abstract:

Objective　To investigate the mechanisms of oxygen free radical/JNK signaling pathway on nerve injury after different degree of intermittent hypoxia (IH) in rats.　Methods　one hundred and sixty Male Sprague-Dawley rats were randomly divided into four groups: control group（n=40），mild intermittent hypoxia group（n=40）, moderate intermittent hypoxia group（n=40），severe intermittent hypoxia group（n=40）. Rats in the control group were exposed in the air，the three intermittent hypoxia groups were exposed respectively in different intermittent hypoxia conditions:100 ml/L，75 ml/L and 50 ml/L; 8-hour-intermittent hypoxia everyday; the duration of experiment 2, 4, 6 and 8 weeks, respectively. The morphological changes were observed by electron microscopy；the malondialdehyde (MDA) contents in cortex were measured with spectrophotometry；the expressions of phosphorylated JNK and c-fos proteins were detected with immunohistochemistry and Western-Blot. The quantity of apoptotic cells was measured by terminal deoxynucleotidyl transfernase medicated nick end labeling (TUNEL) method.　Results　Compared with the control group，the ultrastructure of nerve cell nucleus was injured more severely and the phosphorylated JNK and c-fos expressions and TUNEL-positive cells numbers increased obviously in a time-dependant manner. Moreover, the abovementioned changes were more significant in severe intermittent hypoxia group. The MDA level，phosphorylated JNK and c-fos expressions and TUNEL-positive cells numbers reached peak at 6 weeks in the mild and moderate intermittent hypoxia groups and there were no significant difference between the two group； The MDA level，phosphorylated JNK and c-fos expressions and TUNEL-positive cells numbers reached peak at 8 weeks in severe intermittent hypoxia group and there was significant difference when compared with the mild or moderate intermittent hypoxia groups.　Conclusions　After intermittent hypoxia，oxygen free radical activated ERK1/2 signaling pathway played an important role in the process of nerve cell apoptosis by regulating c-fos expression.

Key words: Intermittent hypoxia, MAP-activated protein kinases, Immunohistochemistry, Western blot, Rat