MK-801诱导精神分裂症小鼠的c-Fos及NADPH氧化酶通路机制研究

Involvement of c-Fos and NADPH Oxidase Pathway in the Pathogenesis of Schizophrenia in Mice Induced by MK-801

目的:探讨MK-801诱导的精神分裂症小鼠的相关机制,为相关精神分裂症的临床研究和治疗提供参考。方法:60只昆明小鼠随机分为3组:对照组、低剂量模型组和高剂量模型组(n=20)。采用两个剂量NMDA受体拮抗剂MK-801建立谷氨酸低下精神分裂症小鼠模型,Western Blot分析小鼠海马组织中相关蛋白c-Fos及NADPH氧化酶亚基(p22、p47、p67)的表达变化。结果:低剂量MK-801能够显著增加模型组小鼠的自发活动及刻板行为,且与对照组相比有显著的统计学差异性(P<0.01),c-Fos蛋白及NADPH氧化酶蛋白亚基p22和p47的表达均明显高于对照组(P<0.01)。而高剂量的MK-801对小鼠具有后肢肌力障碍方面的毒性作用。结论:低剂量的MIK-801能诱导小鼠精神分裂症模型,且氧化应激及c-Fos的过表达参与了MK-801诱导的小鼠精神分裂症的发病过程。

Objective： To explore the pathogenesis mechanism of schizophrenia induced by MK-801 in order to provide reference for clinical research and treatment. Methods： Mice were divided into 3 groups, control group, low dose group and high dose group （n-20）. The schizophrenia mice model was established by injecting MK-801, and the expression of c-Fos and NADPH oxidase units was detected by Western blot. Results： The activity distance and stereotyped behavior were enhanced in the low dose and high dose of MK-801 group （P〈0.01）, and the expression of c-los, and the NADPH oxidase units, p22 and p47 were upregulated greatly compared with control group （P〈0.01）. But high dose of MK-801 indicated toxic role for myodynamia disorder of legs. Conclusion： c-Fos overexpression and oxidative stress participated in the pathogenesis of schizophrenia in mice induced by MK-801.