Objective To explore the effect of inhibitor of MEK/ERK pathway on the behaviors of autistic rats .Methods Autistic rats were made by intraperitoneal injection of sodium valproate (VPA) after pregnancy for 12 .5 days .After VPA injec-tion ,pregnant rats were treated with U0126 via oral at 400 μg/kg dose per day until weaning .Young rats were divided to 4 groups :control group ,VPA group ,U0126 group ,VPA combined U0126 group .The social interaction and behaviors of young rats were e-valuated at 35 days after bornning .The levels of MEK and phosphorylated ERK in brain tissues were investigated by Western blot . Results The autistic rat mode was prepared successfully .Compared with control rats ,the rats treated with VPA showed low the social interaction ,long moving time in central area and reducing standing times .Treatment with U0126 alone didn′t change the so-cial interaction and behaviors of young rats ,but VPA combined U0126 group could improve VPA-induced autistic-like behaviors . Western blot results show that compared with the control group ,the rats treated with VPA could enhance the prefrontal cortex of rats ,the hippocampus and cerebellum in the organization of MEK and ERK phosphorylation level ;while VPA combined U0126 group could inhibit the brain tissue of MEK and ERK phosphorylation level .Conclusion U0126 can improve the model rats of au-tism disorders behavior ,the mechanism may be related to the inhibition of MEK/ERK signaling pathway in the brain .%目的：探讨抑制 MEK ／ERK 通路对孤独症模型大鼠病症行为的影响。方法大鼠怀孕12．5 d 后采用一次性腹腔注射丙戊酸钠（VPA）制备孤独症幼大鼠模型。 U0126处理组于 VPA 注射后每天给大鼠口服400μg／kg MEK ／ERK 通路抑制剂U0126直至断奶。将出生幼鼠分为4组：对照组、VPA 处理组、U0126处理组、VPA 联合 U0126处理组。在幼鼠出生后35 d 进行社会交往行为检测、神经行为学检测，并分离提取脑组织蛋白通过 Western blot 分析 MEK／ERK 通路关键蛋白 MEK 与 ERK表达情况。结果与对照组比较，VPA 处理组社会交往能力下降、在中央区活动时间增加、站立次数减少，符合孤独症行为特征；U0126处理组无明显行为学变化；但 VPA 联合 U0126处理组能明显改善 VPA 处理导致的孤独症行为症状。 Western blot 结果显示，与对照组比较，VPA 处理可增强大鼠前额叶、海马及小脑组织中 MEK 与 ERK 磷酸化水平；而 VPA 联合 U0126处理组则能抑制上述脑组织中 MEK 与 ERK 磷酸化水平。结论 U0126可改善孤独症模型大鼠的病症行为，机制可能与抑制脑组织中MEK ／ERK 通路相关。
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