间歇低氧大鼠细胞外信号调节激酶与认知功能变化

发布时间：2018-03-16 19:32

本文选题：间歇低氧　切入点：海马　出处：《中国神经精神疾病杂志》2014年09期 　论文类型：期刊论文

【摘要】：目的探讨间歇低氧对大鼠海马细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)通路及认知功能变化的影响。方法采用大鼠间歇低氧模型,将成年雄性Wistar大鼠(n=48)随机均分为5%间歇低氧组(5%intermittent hypoxia group,5%IH组)和空白对照组(unhandled control group,UC组),每组分别为24只大鼠,分别于间歇低氧第2、4、6、8周后采用Morris水迷宫实验检测大鼠学习记忆功能;免疫组化及免疫印迹法检测大鼠海马区磷酸化P-ERK1/2表达水平、免疫组化检测c-fos蛋白表达水平;TUNEL法检测神经元凋亡情况。结果与UC组比较,5%IH组在2、4、6、8周大鼠逃避潜伏期时间分别为(50.22±8.42)s、(57.13±9.06)s、(67.56±5.42)s、(71.71±5.49)s,从第2周起随低氧时间延长大鼠逃避潜伏期时间延长(P0.05),5%IH组在2、4、6、8周大鼠跨越目标象限时间分别为(46.23±3.68)s、(39.36±3.42)s、(33.35±4.01)s、(26.82±4.30)s,从第2周起随低氧时间延长大鼠跨越目标象限时间缩短(P0.05),5%IH组p-ERKl/2、c-fos蛋白表达及凋亡指数在2、4、6、8周均多于UC组(P0.05),5%IH组p-ERKl/2、c-fos蛋白表达及凋亡指数均有明显的时间差异性(P0.05),均随间歇低氧时间的延长其表达先升高后降低,6周达到高峰(P0.05),8周逐渐下降(P0.05);UC组p-ERKl/2、c-fos蛋白表达及凋亡指数无时间差异性(P0.05),5%IH组p-ERKl/2与c-fos蛋白的阳性表达相对值呈正相关(r值为0.977,P0.05),c-fos蛋白的阳性表达相对值与神经元凋亡指数呈正相关(r值为0.963,P0.05)。结论ERK通路的激活可能是OSAHS大鼠早中期认知功能损害发生的重要机制。
[Abstract]:Objective to investigate the effects of intermittent hypoxia on extracellular signal-regulated kinases (ERK) pathway and cognitive function in rat hippocampus. Adult male Wistar rats were randomly divided into 5% intermittent hypoxia group (n = 5) and a blank control group (n = 24). The rats in each group were randomly divided into two groups: the control group (n = 24) and the control group (n = 24). Morris water labyrinth test was used to detect the learning and memory function of the rats after 68 weeks of intermittent hypoxia. The expression of phosphorylated P-ERK1 / 2 in hippocampus of rats was detected by immunohistochemistry and Western blotting. Results compared with UC group, the escape incubation period of rats in 5IH group was 50.22 卤8.42% and 67.56 卤5.42 sago respectively, and the escape latency was prolonged with hypoxia time from the 2nd week to the second week. The time of crossing the target quadrant was 46.23 卤3.68 ~ 39.36 卤3.42 ~ 39.36 卤3.42 in the P0.05 / 5IH group, respectively. The expression of p-ERKl-c-fos protein and the apoptosis index in the p-ERKl-2c-fos group were more than those in the P0.05IH group at 2468 weeks with the prolongation of the time of crossing the target quadrant from the second week. The expression of p-ERKl- c-fos protein and the apoptosis index in the P0.05IH group were higher than those in the UC group P0.055IH group with the prolongation of the time of crossing the target quadrant from the 2nd week to the end of the second week. The expression of p-ERKl- 2c-fos protein and the apoptosis index of the rats in the P0.05IH group were higher than those in the UC group at 2468 weeks. White expression and apoptosis index were significantly different in time. With the prolongation of intermittent hypoxic time, the expression of white protein increased first, then decreased to the peak at 6 weeks. The expression of p-ERKl / 2nc-fos protein and apoptosis index in UC group decreased gradually after 8 weeks. There was no significant difference in P0.055and IH. The positive correlation between the expression of p-ERKl / 2 and c-fos protein was positively correlated with the expression of c-fos protein. The positive correlation between the expression of p-ERKl / 2 and the expression of c-fos protein was 0.977P0.05and the neuron apoptosis index. Conclusion the activation of ERK pathway may be the cognitive impairment of OSAHS rats in early and middle stage. An important mechanism for the occurrence of damage.
【作者单位】：河北联合大学附属医院呼吸科;
【基金】：河北省高等学校科学技术研究重点项目河北省重大课题资助项目河北省自然科学基金资助项目(编号:ZH2011120;zd2013091;H2014209231)
【分类号】：R766

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