目的 观察孤独症大鼠前额叶皮质中Notch信号通路相关蛋白发状分裂相关增强子(Hes1)和星形胶质细胞标记物胶质纤维酸性蛋白(GFAP)的变化，探讨Notch信号通路在孤独症发病机制中的作用。方法 健康繁殖期Wistar雌鼠20只，体重250~260 g，随机选取15只在妊娠12.5 d(E12.5)腹腔注射丙戊酸钠(VPA)，其子代为孤独症模型组;其余5只则注射等量生理盐水，子代为对照组。通过比较三箱实验、自梳理实验验证模型建立是否成功;Western blot方法对比孤独症模型组与对照组大鼠出生后42 d(P42)前额叶皮质中Hes1以及GFAP表达水平的变化。结果 1)成功建立孤独症动物模型:与正常对照组比较，三箱实验显示模型组大鼠交互能力障碍、缺乏对新鲜事物的偏好性;自梳理实验显示模型组理毛时间显著增加(P<0.05);2)与正常组比较，模型组大鼠P42前额叶皮质Hes1表达显著升高(P<0.05)，GFAP表达显著升高(P<0.05)。结论 孤独症大鼠P42前额叶皮质Notch信号通路活化增多，且伴星形胶质细胞增多，提示孤独症的发病机制可能与Notch信号通路的异常活化有关。
Abstract
Objective To investigate the changes of Notch-related protein hairy and enhancer of split 1 (Hes1) and astroglia marker glial fibrillary acidic protein (GFAP) and discuss effect of Notch signals in the rat model of autism. Methods Fifteen female Wistar rats (250~260 g) out of 20 were selected randomly to receive a single intraperitoneal injection of sodium valproate (VPA) at embryonic day 12.5(E12.5),and their offspring were defined as the autism model group.The rest 5 female Wistar rats received the intraperitoneal injection of saline,and their offspring were defined as the control group.The successfully animal model was confirmed by the three-chamber sociability test and self-grooming test.Western blotting was used to detect the expression of Hes1 and GFAP in prefrontal cortex in the two group on postnatal day 42(P42). Results 1)The animal model of autism was successfully established.Compared with the control group,the sociability and preference for social novelty were significantly decreased,and the cumulative self-grooming time in the autism model group significantly increased (P<0.05).2)Compared with the control group,Hes1 and GFAP expression significantly increased in prefrontal cortex of the autism model group on P42 (P<0.05). Conclusion In prefrontal cortex of the rat model of autism,activation of Notch signaling increased,moreover,the number of astrocyte also increased,which suggest the pathogenesis of autism may involve Notch signal in the prefrontal cortex.
关键词
孤独症 /
Notch /
发装分裂相关增强因子 /
胶质纤维酸性蛋白
Key words
autism /
Notch /
hairy and enhancer of split 1 /
glial fibrillary acidic protein
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基金
贵阳市科技计划项目[筑科合同(2011103)18号];贵州省科技攻关计划课题[黔科合SY(2010)3082号]
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