CHOP 在间歇低氧大鼠认知功能减退中的表达及意义

摘要

目的：探讨 C/EBP 同源蛋白(CHOP)在间歇性低氧大鼠认知功能减退中的表达变化及其意义。方法将75只雄性 Wistar 大鼠随机分为正常组(NC 组)、5%间歇低氧组(5% CIH 组)、10%间歇低氧组(10% CIH 组),每组25只；每组又各分为3、7、14、21、28 d 时间亚组,每个时间亚组5只。正常组暴露于空气中,间歇低氧组分别暴露于间歇性低氧条件下(暴露时间每天8 h,持续时间3、7、14、21、28 d)。采用 Morris 水迷宫检测大鼠学习记忆功能,免疫组化检测海马 CA1区 CHOP 表达,TUNEL 法检测海马 CA1区神经细胞凋亡。结果①与 NC 组比较,2个 CIH 组动物逃避潜伏期随低氧时间的延长而延长(P <0.05),跨越目标象限的时间随低氧时间的延长而缩短(P <0.05),海马神经元凋亡指数随缺氧时间的延长均逐渐升高(P <0.05)；与10% CIH 组比较,5% CIH 组上述变化有统计学意义(P <0.05)。②与 NC 组比较,2个 CIH 组 CHOP 蛋白的表达随缺氧时间的延长于各个时间点均增加(P <0.05),其中10% CIH 组于28 d 达峰,5% CIH 组于21 d 达峰后下降。③双变量相关分析显示,2个 CIH 组其 CHOP 表达与凋亡指数、动物逃避潜伏期时间均呈正相关,与跨越目标象限时间均呈负相关。结论间歇性低氧可以引起不同程度的认知功能减退,可能与其诱导 CHOP 高表达并激活 CHOP 介导的神经细胞凋亡密切相关。%Objective To explore the expression changes of C/EBP homologous binding protein (CHOP)in intermittent hypoxic rats with cognitive function decline and clinical significance.Methods We randomly divided 75 adult male Wistar rats into normal group (NC group),5% intermittent hypoxia group (5% CIH group)and 10%intermittent hypoxia group (10% CIH group),with 25 rats in each.Then the three groups were further divided into 3 d,7 d,14 d,21 d and 28 d subgroups,and each time a subgroup had 5 rats.The control group was exposed to the air while 10% CIH group and 5% CIH group were exposed to CIH for eight hours from 8:00 to 1 6:00 each day. After exposure for 3 d,7 d,14 d,21 d and 28 d,the cognitive function of rats was assessed with Morris water maze, the expression of CHOP in the hippocampus was assayed qualitatively by immunohistochemical technique,and the apoptosis of neurons was detected by TUNEL method.Results ① With prolonged hypoxia,the time of escape latency obviously prolonged,the time spent crossing the target quadrant shortened (P < 0.05 ),and the apoptosis index of hippocampal neurons in the CIH groups was increased gradually compared with those in control group (P <0.05).The above-mentioned indexes changed more significantly in 5% CIH group than in 10% CIH group (P <0.05).②.The expression of CHOP protein at each time point was increased (P <0.05 ).In 10% CIH group it reached the peak at 28 d while in 5% CIH group it decreased after it peaked at 21 d.③ The expression of CHOP in the two CIH groups was positively correlated with apoptosis index and animal escape latency time,but negatively correlated with the target quadrant time.Conclusion Intermittent hypoxia,which is likely to induce the high expression of CHOP and activation of neural CHOP mediated apoptosis,causes cognitive impairment of various degrees.