Abstract:

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 intermittenthypoxia conditions（100，75 and 50 mL/L,8 h everyday for 8 weeks).Theexpression 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(P<0.05)；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(P<0.05).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(P>0.05)；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(P<0.05).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.

Key words: mitogen-activated protein kinases；apoptosis, immunohistochemistry；Western blotting method；rats,SD, intermittent hypoxia