The Influence On Memory Functions And Expression Of JNK Protein At Hippocampus In Rat Exposed Under Varying Degree Of Chronic Intermittent Hypoxia

Objective A animal model of chronic intermittent hypoxia was set up to simulate the features of OSAHS(Obstructive Sleep Apnea Hypopnea Syndrome ) ,which was to observe the learning and memory changes and explore the expression of JNK in neuron of hippocampus in the rat.Methods Adult male Wistar rats (n = 144) were randomly divided into 5% of chronic intermittent hypoxia group (5%CIH group), 10% of chronic intermittent hypoxia group (10%CIH group) and control group (UC group).Rats in every groups were raised normally, and then those in CIH groups suffered 8 hours intermittent hypoxia everyday, the duration of experiment was respectively 2^nd, 4^th, 6^th and 8^thweek. The compressed air was given to the UC group. The learning and memory ability of rats in each group was assessed with the Morris water maze(MWM) test at the end of the experiments, the levels of superoxide dismutase(SOD) and malondialde--hyde(MDA) were detected by colorimetric method .Immunohistochemistry and Western blotting were used to examine the expression of JNK protein in the hippocampus of ratsStatistical analysis SPSS13.0 statistical package was used for data analysis, the data with mean±standard deviation ((x|-)±s). One-Way ANOVA was used to the comparison between groups, LSD method was used on multiple comparisons, P <0.05 was considered statistically significant.Results1 Morris water maze experimental results The comparative in different time within group: with the extension of time, the escape latency of rats was significantly longer and the times of crossing the platform decreased in CIH group ,which displayed significant difference in 10%CIH groups in 2^nd, 4^th and 6^th week(P<0.05), in 5%CIH group in 2^nd, 4^th, 6^th, 8^th week(P<0.05);The comparative in same time between groups: Compared with UC group, rats in CIH groups showed escape incubation period time obvious extended and the time of through original platform location significantly reduced. There was different in time that change starting, in 5%CIH group, it was occurred at the 2^nd week, while in the 10%CIH group, at 4^th week. Those changes were significant at 6^th week. Compared with 10%CIH group, the escape latency of rats was significantly longer and the times of crossing the platform decreased in 5%CIH group in 2^nd, 4^th, 6^th, 8^th week, which displayed significant difference(P<0.05).2 Comparing with UC group, the activity of SOD in the hippocampal region group was lower significantly (P<0.05) and the level of MDA was higher significantly(P<0.05) in 5%CIH and 10%CIH, along with the time expand, which aggravated.3 Phosphorylation JNK (p-JNK) immunohistochemical results Most of the nuclear of positive cells stained in brown or pale yellow, which were observed under Optical microscope. Rats of each group have positive cells. The degrees of positive cells were different and most of positive cells located in CA1 region of hippocampus. The comparative in different time within group :In 10% CIH group and 5%CIH group, p-JNK positive cells in hippocampus increased markedly in 2^nd, 4^th, 6^th, 8^th week, to the peak at 6^th week, there was no significant difference between 6^th week and 8^th week; the comparative in same time between groups: compared with UC group-JNK positive cells in hippocampus increased markedly in CIH groups (P<0.05);compare with 10%CIH, 5%CIH in the 2^nd,4^th,6^th,8^th, p-JNK positive cells in hippocampus increased significantly(P<0.05).4 p-JNK Western blot results The comparative in different time within group:10%CIH group of animals and 5%CIH group in 2^nd, 4^th, 6^th, 8^th week, phosphorylation JNK expression in hippocampus increased markedly, reaching to the peak in the 6^th week;the comparative in same time between groups: compared with the UC group, p-JNK positive cells in hippocampus increased significantly in CIH groups; compared with the 10%CIH group, 5%CIH group in 2^nd, 4^th, 6^th, 8^th week, p-JNK positive cells in hippocampus increased significantly(P<0.05).Conclusion1 Chronic intermittent hypoxia can make the function of learning and memory in rats. With the extension of exposure time and the aggravation of exposure density, the function of learning and memory presents the gradually aggravating trend. The rats exposed under serious chronic intermittent hypoxia presented obvious cognitive impairment at 2^nd week.2 Comparing with UC group, the activity of SOD in the hippocampal region was significantly lower and the level of MDA group was significantly higher in CIH groups.3 p-JNK Positive cells were located in nuclear in CIH group mostly,most of positive cells were in CA1 of hippocampus. With low oxygen degree of aggravating, the expression of p-JNK protein in rat hippocampal organization gets its peak in 6^th week.4 Chronic intermittent hypoxia could result in damage and lesion of spatial learning and memory in rats.It may be correlated with that oxidative stress active JNK MAPK, which caused p-JNK protein expression increased.