亚慢性地卓西平诱导的精神分裂样小鼠前额叶和海马脑区MIF蛋白表达的变化

目的:探讨亚慢性地卓西平(MK-801)诱导的精神分裂样小鼠模型中前额叶和海马脑区巨噬细胞迁移抑制因子(Macrophage migration inhibitory factor,MIF)蛋白表达的变化。方法:将24只7周龄小鼠随机分为对照组、MK-801组和MK-801+奥氮平(olanzapine,olz)组(n=8),三组小鼠分别接受0.9%生理盐水、MK-801(0.6 mg/kg)和MK-801(0.6 mg/kg)+奥氮平(2.5 mg/kg)给药,持续4周。小鼠行为学通过旷场试验、社交实验进行评价,免疫印迹法检测小鼠前额叶和海马组织中MIF蛋白的表达。结果:MK-801处理后,小鼠活动量增加,社交功能受损,且都能被抗精神分裂症药物奥氮平显著改善。MK-801组小鼠前额叶皮层中MIF蛋白表达与对照组比较无明显统计学差异(P0.05),而海马脑区中MIF蛋白表达较对照组明显升高(P0.05);MK-801+奥氮平组小鼠前额叶皮层中MIF蛋白表达较MK-801组无显著变化,而海马脑区中MIF蛋白表达较MK-801组明显降低(P0.05)。结论:亚慢性给予MK-801诱导的精神分裂样小鼠海马脑区中MIF蛋白水平升高,提示MIF蛋白可能参与MK-801诱导的精神分裂样行为。

Changes of MIF Protein Expressions in the Prefrontal Cortex and Hippocampus of Subchronic Injection of Dizocilpine Induced Schizophrenia Mice

Objective:To investigate the changes of MIF protein expressions in prefrontal cortex and hippocampus in the subchronic injection of dizocilpine (MK-801) induced schizophrenia mice.Methods:24 mice were randomly divided into 3 groups: control group, MK-801group, and MK-801+ olanzapine group (n=8), treated with saline (0.9%), MK-801(0.6 mg/kg), and MK-801 (0.6 mg/kg) + olanzapine (2.5 mg/kg) for 4 weeks, respectively. Open field and social behavior test were conducted to evaluate the schizophrenia-like behavior phenotype of the mice. The content of MIF protein in prefrontal cortex and hippocampus was determined by western blot analysis.Results:The locomotor activity of mice increased and the social function was impaired after treated with MK-801, which could both be reversed by olanzapine. Compared with control group, MIF protein level was elevated in hippocampus after MK-801 treated mice (P<0.05), while had no significant change in PFC (P>0.05). Compared with MK-801 group, MIF protein level was elevated in hippocampus in MK-801+olanzapine group (P<0.05), which had no significant change in PFC either (P>0.05).Conclusion:MIF protein level was elevated in hippocampus of MK-801 induced mice model of schizophrenia, which indicated that MIF may be involved in MK-801 induced schizophrenia-like behavior in C57BL/6 mice.