地卓西平马来酸盐精神分裂症模型大鼠前额叶皮质与外周神经调节蛋白-1基因表达的关系

The relationship of neuregulin-1 gene expression between prefrontal cortex and periphery in MK-801 schizophrenic model rat

目的了解sD大鼠神经调节蛋白-1（Nrg1）基因mRNA在地卓西平马来酸盐（MK-801）作用下的表达变化及氯氮平干预的影响，初步探讨Nrgl基因mRNA在大鼠前额叶皮质和外周表达变化关系。方法采用MK-801对66只清洁级雄性SD大鼠建立大鼠精神分裂症模型，分为模型组（30只）、对照组（30只）和干预组（6只）。采用SMART小动物行为视频分析系统测定3组大鼠的自发活动，并对大鼠刻板行为和共济失调等行为进行评分；应用实时荧光定量逆转录-聚合酶链反应同时检测不同时间点3组大鼠中枢前额叶皮质与外周血淋巴细胞Nrg1基因mRNA的表达水平。结果3组大鼠自发活动结果、共济失调评分、刻板行为评分差异均有统计学意义（F：14．905，P=0．000；F=76．196，P=0．000；F=72．654，P=0．000）。与对照组比较，模型组外周总Nrg1 mRNA（t=2．779，P=0．019）和前额叶皮质人神经调节蛋白（Hrg）mRNA（t=2．293，P=0．045）在药物作用90min时表达增高，外周胶质生长因子（Ggf）mRNA在120min时表达增高（t=2．728，P=0．035）；在90min时，干预组外周GsfmRNA（F=4．484，P=0．030）表达低于模型组，模型组前额叶皮质HrgmRNA（F=4．238，P=0．035）的表达高于对照组和干预组，模型组和对照组前额叶皮质感觉-运动神经元衍生因子mRNA（F=4．739，P=0．025）的表达高于干预组。大鼠自身前额叶皮质与外周血淋巴细胞中总NrglmRNA表达呈正相关（r=0．252，P=0．041）。结论MK-801可以影响部分Nrg1亚型mRNA表达，氯氮平能够部分减弱这种影响；大鼠总Nrg1mRNA外周与前额叶皮质的表达具有一致性，外周血总Nrg1mRNA表达情况可以在一定程度上反映前额叶皮质的变化。

Objective To investigate the effect of MK-801 and clozapine on the expression levels of Nrg-1 mRNA in SD rats. The relationship of Nrgl gene mRNA expression between prefrontal cortex and periphery in rats was preliminarily discussed. Methods Sixty-six male SD rats were divided into 3 experimental groups, 30 were given MK-801 as model group, 30 given saline as control group and 6 given clozapine ＋ MK-801 as intervention group. The Nrgl gene mRNA expression in the central prefrontal cortex and peripheral blood lymphocytes at different time points was assayed with semi quantitative RT- PCR. Results Significant differences on locomotion distance, a taxia score and stereotype scores existed among model group, control group and intervention group （P 〈 0. 001 ）. Within model group, the expression of peripheral total Nrgl mRNA was significantly higher than that in control group at 90 minute after medication （t = 2. 779, P = 0. 019）. The expression of peripheral ggf mRNA were significantly higher than that in control group at 120 minute after medication （ t = 2. 728, P = 0. 035 ）. The expression of central hrg mRNA were significantly higher than that in control group at 90 minute after medication （t=2. 293, P = 0. 045 ）. Significant positive correlation existed between prefrontal cortex total Nrgl mRNA and peripheral blood lymphocytes （r = 0. 252, P =0. 041 ）. Conclusions Schizophrenia-like behavior induced by MK-801 in rats could be partly improved by clozapine. Nrgl gene mRNA expression could be partly affected by MK-801, which could be attenuated by clozapine. The expression variations in peripheral blood total Nrgl mRNA could reflect the change in central ones.