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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250~260g,随机选取15只在妊娠12.5d(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42d(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。
Objective To observe the changes of Notch signaling-related protein hairpin-split-related enhancer (Hes1) and glial fibrillary acidic protein (GFAP) in the prefrontal cortex of autistic rats and to explore the role of Notch signaling pathway in autism The role of pathogenesis. Methods Twenty healthy Wistar female mice weighing 250-260g were enrolled in this study. Fifteen randomly selected mice were injected intraperitoneally with sodium valproate (VPA) at 12.5 d of gestation (E12.5), and their offsprings were autistic model group. The remaining five The same amount of saline injection, offspring for the control group. By comparing the three-box experiment, the establishment of the model was verified by combing experiments. The expression of Hes1 and GFAP in the prefrontal cortex of 42 d after birth (P42) in the autism model group and the control group were compared by Western blot. Results 1) Animal model of autism was successfully established: Compared with the normal control group, the three-box experiment showed that the rats in the model group had poor interaction ability and lacked the preference for new things; the combing experiments showed that the grooming time of the model group increased significantly (P < 0.05) .2) Compared with normal group, the expression of Hes1 in P42 prefrontal cortex in model group was significantly increased (P <0.05) and GFAP expression was significantly increased (P <0.05). Conclusions The activation of Notch signaling pathway in P42 prefrontal cortex and the increase of astrocytes in autistic rats suggest that the pathogenesis of autism may be related to the abnormal activation of Notch signaling pathway.