常压高氧处理对丙戊酸钠孤独症模型鼠学习记忆能力及海马CA1区锥体细胞形态学的影响

Effects of normobaric hyperoxia on the learning and memory abilities of valproic acid autism model rats and the morphology of pyramidal cells in hippocampal CA1 region

目的探讨常压高氧处理对丙戊酸钠（VPA）孤独症模型鼠学习记忆能力及海马CA1区锥体细胞形态学的影响。方法Wistar大鼠怀孕第12．5天腹腔注射600mg／kgVPA后所产下的子代雄鼠，根据子鼠睁眼时间、行为表现、断乳时体质量，结合生后第28天采用Y型电迷宫测试其学习记忆能力，获得40只造模成功的孤独症模型雄鼠，随机选取20只分为常压高氧模型组（A组）、常压空气模型组（B组），每组10只；选取Wistar孕鼠同期腹腔注射等量生理盐水后所产下的10只子代雄鼠作为常压空气正常组（C组）。A组每日1h，持续7d常压高氧治疗；B、C组常规喂养。3组子代雄鼠生后35d时复测其学习记忆能力，并采用免疫组化和图像分析技术检测模型鼠海马CA1区锥体细胞形态学改变。结果常压高氧处理孤独症模型鼠Y型电迷宫测试的尝试次数少于治疗前尝试次数[（31．15±0．99）次，（31．54±0．97）次，（t=2．739，P=0．018）]，再现次数多于治疗前再现次数[（3．00±0．58）次，（2．69±0．48）次，t=-2．309，P=0．040]。A组治疗后尝试次数少于B组同期尝试次数（t=2．583，P=0．016），再现次数与B组同期无差异（t=0．244，P=0．810）。孤独症模型鼠海马CA1区锥体神经元细胞发生凋亡，常压高氧处理后细胞凋亡减少、正常形态细胞数增多。结论常压高氧处理可以提高丙戊酸钠孤独症模型鼠的学习记忆能力，减少海马CA1区锥体神经元凋亡。

Objective To investigate the effects of normobaric hyperoxia intervention on learning and memory abilities of valproic acid（VPA） autism model rats and the morphology of pyramidal cells in hippocampus CA1 area. Methods Animal model groups of autism were obtained in male offspring of the Wistar rats that received intraperitoneal injection of 600 mg/kg VPA at the 12.5 day after pregnancy. According to the eye opening time,behavior,weaning weight and the learning and memory abilities which were evaluated by the Y electricity maze test at the 28th day after birth ,40 male VPA autism model rats were randomly selected 20 only and divided into normobaric hyperoxia model group （group A, n = 10 ）, atmospheric air model group （group B, n = 10 ）. Normal control groups were obtained in male offspring of Wistar rats that received intraperitoneal injection of equivalent physiological saline at the same period pregnancy. （group C, n= 10）. Rats in group A were treated with oxygen for 1 h per day and lasted 1 week;group B and C were treated with normal air. The learning and memory abilities of three groups were assessed at the 35th day after birth. The immunohistochemistry methods and image analysis were used to observe the pyramidal cells of autism model rats in hippocampal CA1 region. The effect of normobaric hyperoxia therapy on pyramidal cell of autism model rats in hippoeampal CA1 region were evaluated by HE staining technique. Results The trying times of group A after treatment were less than those before treatment （31.15 ± 0. 99 vs 31.54 ±0. 97, t = 2. 739, P = 0. 018 ）. The memory times were more than those before treatment （ 3.00 ± 0.58 vs 2.69 ± 0.48, t = - 2. 309, P = 0. 040）. The trying times of group A after treatment were less than those in group B after treatment（P=0. 016）. The memory times of group A were not different from that in group B after treatment （P = 0. 810）. The morphology of pyramidal cells in hippocampal CA1 region showed that the pyramidal cells of the autism model rats had apoptosised. The number of apoptotic cells reduced and the number of normal form cells increased after the normobaric hyperoxia intervention compared with the autism model rats. Conclusion Normobaric hyperoxia intervention can improve the learning and memory abilities of the autism model rats. The apoptosis of the pyramidal neurons in hippocampal CA1 might be reduced after the normobaric hyperoxia intervention.