不同程度间歇性低氧大鼠海马区磷酸化JNK的表达及其意义

目的：探讨不同程度间歇性低氧大鼠海马区磷酸化JNK表达水平变化，阐明低氧大鼠认知功能障碍的发生机制。方法：96只雄性SD大鼠随机分成对照组和轻、中、重度间歇低氧组，每组24只。对照组大鼠暴露于空气中，不同程度间歇低氧组大鼠分别暴露于不同低氧条件（100、75和50 mL/L，暴露时间每天8 h，持续8周）。采用Western blotting和免疫组织化学法检测大鼠海马区磷酸化JNK蛋白表达水平；采用原位缺口末端标记（TUNEL）法检测各组大鼠凋亡细胞数量；采用Morris水迷宫法检测各组大鼠学习记忆功能。结果：与对照组比较，随低氧时间的延长，轻、中、重度间歇性低氧组大鼠海马区磷酸化JNK阳性细胞数和JNK蛋白表达水平均增加(P<0.05)，TUNEL阳性细胞增多（P<0.05）；水迷宫法检测，轻、中、重度间歇性低氧组大鼠逃避潜伏期时间延长和穿台次数减少（P<0.05）。与轻、中度间歇性低氧组比较，在重度间歇性低氧组TUNEL阳性细胞数增多，JNK蛋白表达水平和大鼠逃潜伏期延长，穿台次数减少（P<0.05）；轻、中度间歇性低氧组磷酸化JNK表达水平和TUNEL阳性细胞6周时达高峰，8周时降低，但组间各时间点比较差异无统计学意义(P>0.05)；重度间歇性低氧组磷酸化JNK表达水平和TUNEL阳性细胞8周时达高峰，组间各时间点比较差异有统计学意义(P<0.05)。结论：不同程度间歇性低氧可导致大鼠认知功能损伤，其机制与激活大鼠海马区JNK、调控神经细胞凋亡有关。

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(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.