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| 舒林酸对孤独症模型大鼠病症行为的改善作用 | |
| 引用本文： | 秦利燕,戴旭芳. 舒林酸对孤独症模型大鼠病症行为的改善作用[J]. 南方医科大学学报, 2015, 35(8): 1162 |
| 作者姓名： | 秦利燕 戴旭芳 |
| 摘 要： | 目的探讨舒林酸对孤独症模型大鼠病症行为的改善作用。方法在大鼠怀孕12.5 d 后采用一次性腹腔注射丙戊酸钠 （VPA）制备孤独症大鼠模型。针对舒林酸处理组，于VPA注射后每天给大鼠口服20 mg/kg舒林酸直至断奶。将出生幼鼠分为 4组：对照组，VPA处理组，舒林酸处理组及VPA联合舒林酸处理组。出生后35 d对幼鼠进行社会交往行为检测、敞箱焦虑样行 为检测，并分离提取脑组织蛋白利用Western blot分析Wnt信号通路关键蛋白β-catenin与Gsk3β表达情况。结果成功制备孤独 症大鼠模型。与对照组相比，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；舒 林酸单独处理组无明显行为学变化；但舒林酸联合处理能明显改善VPA处理导致的孤独症行为症状。Western blot结果显示， 与对照组相比，VPA处理可增强大鼠前额叶、海马及小脑组织中β-catenin表达水平并降低Gsk3β第9位丝氨酸磷酸化水平；而舒 林酸联合处理则能抑制上述脑组织中β-catenin表达水平并增加Gsk3β第9位丝氨酸磷酸化水平。结论舒林酸可改善孤独症模 型大鼠的病症行为，机制可能与抑制脑组织中Wnt信号通路相关。 |
Effect of sulindac on improving autistic behaviors in rats |
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| Abstract: | Objective To test the effect of sulindac on autistic behaviors in a rat model and explore the possible mechanisms. Methods Autistic rat models were established by a single intraperitoneal injection of sodium valproate (VPA) at 12.5 days of pregnancy. The pregnant rats were treated with oral sulindac at a daily dose of 80 mg/kg until weaning of the newborn rats (23 days after being born), which were divided into control, VPA treatment, sulindac treatment, and VPA+ sulindac treatment groups. The social interaction and neuroethology of the newborn rats were evaluated at 35 days, and the levels of β-catenin and phosphorylated Gsk3β in the brain tissues were investigated by Western blotting. Results Compared with the control rats, the rats treated with VPA showed lower social interaction, longer moving time in central area, and reduced standing times. Treatment with sulindac alone resulted in no obvious changes in the social interaction or neuroethology of the newborn rats, but sulindac treatment corrected VPA-induced autistic-like behaviors. Sulindac also attenuated VPA-triggered p-Gsk3β downregulation and β-catenin upregulation in the prefrontal lobe, seahorse and cerebellum. Conclusion Sulindac can improve the behaviors of autistic rats possibly by suppressing Wnt signaling pathway. |
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