舒林酸对丙戊酸孤独症动物模型大鼠氧化应激变化的影响

摘要

[ ABSTRACT] AIM:To investigate the effects of sulindac on oxidative stress in autism.METHODS:With an au-tistic model induced by prenatal exposure to valproic acid ( VPA) , we detected the expression of the signaling molecules of canonical Wnt pathway in the prefrontal cortex ( PFC) and hippocampus ( HC) of autistic rats treated with sulindac.The protein expression levels of glycogen synthase kinase 3β(GSK-3β), β-catenin and 4-hydroxynonenal (4-HNE) were ob-served by Western blotting.The mRNA expression of thioredoxin(Trx)1 and Trx2 was assessed by semi-quantitative RT-PCR.RESULTS:The protein level of GSK-3βand mRNA levels of Trx1 and Trx2 were lower, whereas the protein expres-sion levels ofβ-catenin and 4-HNE were higher in VPA group than those in control group.In contrast, the protein levels of GSK-3βwere significantly higher in the animals treated with both VPA and sulindac than those in VPA group, while the lev-els ofβ-catenin and 4-HNE were decreased.CONCLUSION:Sulindac attenuates oxidative stress in the pathogenesis of au-tism, suggesting the up-regulation of the Wnt/β-catenin signaling pathway disrupts oxidative homeostasis and further facili-tates susceptibility to autism.%目的：探讨舒林酸对孤独症发生过程中氧化应激变化的影响。方法：利用丙戊酸（ VPA）孤独症动物模型，检测经典Wnt信号通路特异性抑制剂舒林酸处理后经典Wnt信号通路及氧化应激标志物在孤独症模型大鼠前额叶皮质及海马脑区的表达变化。 Western blotting法检测糖原合成激酶3β（ GSK-3β）、β-catenin和4-羟基壬烯醛（4-HNE）表达，半定量RT-PCR法检测硫氧还蛋白（Trx）1和Trx2 mRNA表达。结果：与对照组相比，在前额叶皮质及海马脑区VPA组GSK-3β蛋白表达减少， Trx1和Trx mRNA 表达减少，β-catenin与4-HNE的表达增加；而与VPA组相比，VPA与舒林酸同时处理组GSK-3β的表达显著增加，β-catenin和4-HNE的表达显著减少。结论：舒林酸减少了孤独症发生过程中氧化应激的产生，提示经典Wnt信号通路上调导致氧化应激产生，进而导致孤独症易感性增加。