孤独症大鼠海马自噬相关蛋白的表达

目的 探讨细胞自噬在孤独症发病中的作用。 方法 健康繁殖期Wistar雌鼠20只(250～260g)，雄鼠10只(280～290g)，按2∶1比例合笼过夜，次日早上阴道涂片发现精子计为孕1d。在其孕12.5d时，10只雌鼠腹腔注射丙戊酸钠，其子代为孤独症模型组；10只注射同等剂量生理盐水，其子代为正常组。通过比较自梳理实验、三箱实验验证孤独症模型是否成功；Western blotting方法对比正常组与孤独症模型组大鼠生后42d（P42）海马自噬相关蛋白LC3-Ⅱ、Beclin-1和P62表达的变化。 结果 1.成功建立孤独症动物模型,与正常组比较，自梳理实验显示, 模型组理毛时间较正常显著增加（P<0.05），三箱实验结果显示，模型组大鼠交互能力障碍、缺乏对新鲜事物的偏好性；2.与正常组相比较，模型组大鼠P42d海马自噬相关蛋白LC3-Ⅱ表达显著降低（P<0.05），Beclin 1表达显著降低（P<0.05），P62表达显著升高（P<0.05）。 结论 孤独症大鼠P42d海马自噬活性降低，提示增强自噬可能是一个潜在的治疗策略。

Expression of the autophagy-related protein in hippocampus in a rat model of autism

Objective To investigate the effect of autophagy in the rat model of autism. Methods Twenty female Wistar rats (weight 250-260g) were mated with 10 male (weight 280-290g) overnight, and in the morning when spermatozoa were found it was designated as the first day of gestation. Females received a single intraperitoneal injection of sodium valproate on the 12.5 day after conception, and control females were injected with physiological saline at the same time. The offspring of valproate-treated females were model group, and the offspring of physiological saline -treated females were control group. The self-grooming test and three-chambered social test were used to confirm whether the autism model were successful. Western blotting was used to detect the expressed level of LC3-Ⅱ, Beclin 1 and P62 in hippocampal of eatch group. Results 1.The animal model of autism was successfully established. Compared with the control group, the cumulative self-grooming time was significantly increased（P<0.05）, the sociability and preference for social novelty were significantly decreased（P<0.05）. 2. Compared with normal control group, the model group significantly decreased the expression level of LC3-Ⅱ（P＜0.05）and Beclin 1（P＜0.05）in hippocampal. Meanwhile the expression level of P62 was significantly increased（P＜0.05）. Conclusion The present findings confirmed that the autophagy is inhibitied in hippocampus of autism, which suggests modulation of autophagy might be a potential therapeutic strategy for autism.