Expression of phosophorylated JNK in hippocampus of rats with different degrees of intermittent hypoxia and its significance

Objective To investigate the changes of expression levels of posophorylated JNK in hippocampus of rats with different degrees of intermittent hypoxia and to clarify the mechnism of cognitive dysfunction of hypoxia rats.Methods 96 male SD rats were randomly divided into control group(n=24),mild intermittent hypoxia group(n=24),moderate intermittent hypoxia group(n=24) and severe intermittent hypoxia group(n=24).The rats in control group were exposed in air,and the rats in intermittent hypoxia groups were exposed respectively in different intermittent hypoxia conditions(100,75 and 50 mL·L-1,8 h everyday for 8 weeks).The expression levels of phosphorylated JNK proteins were detected by immunohistochemistry and Western blotting methods;the number of apoptotic cells was measured by terminal deoxynucleotidyl transfernase medicated nick end labeling(TUNEL) method;the learning and memory functions were determined by Eight-arm maze.Results Compared with control group,the expression levels of phosphorylated JNK and the number of TUNEL-positive cells in intermittent hypoxia groups were increased obviously in a time-dependant manner(P0.05);Water maze test showed that the escaping latency was prolonged and the frequency of crossing the platform was decreased in a time-dependant manner in mild,moderate and severe interminttent hypoxia group.Compared with mild,moderate intermittent hypoxia groups,the number of TUNEL positive cells was increased;the expression level of JNK protein was increased and the escaping latency was prolonged and the frequency of crossing the platform was decreased in severe intermittent hypoxia group(P0.05).The expression levels of phosphorylated JNK and the numbers of TUNEL-positive cells reached peak at 6 weeks and reduced at 8 weeks in mild and moderate intermittent hypoxia groups and there were no significant difference between different time points in two groups(P0.05);the expression level of phosphorylated JNK and the number of TUNEL-positive cells reached peak at 8 weeks in severe intermittent hypoxia group and there were significant differences between different time points in sever intermittent hypoxia group(P0.05).Conclusion Different degrees of intermittent hypoxia can cause cognitive dysfunction and its mechanism may be related to activating JNK in hippocampus of rats and regulating the neuronal apoptosis.