精神分裂症模型大鼠神经调节蛋白1基因的表达分析

目的 探讨地卓西平马来酸盐( dizocilpine maleate,MK801)精神分裂症大鼠外周血淋巴细胞与中枢不同脑区神经调节蛋白1基因表达变化及中枢与外周表达的一致性.方法 30只成年雄性SD大鼠随机分为3组,实验组(按100 μl/20g体质量分别于右后侧腹腔注射0.6mg/kg剂量的MK-801,又称模型组)、对照组1(不做任何处理)和对照组2(注射等体积生理盐水),每组各10只,应用半定量RT-PCR方法测定3组外周血及中枢前额叶区Nrg1mRNA表达水平,应用免疫组织化学方法测定中枢前额叶区、齿状回区及海马区Nrg1蛋白表达水平.结果 3组大鼠中枢及外周Nrg1mRNA表达均差异有显著性(中枢F=9.141,P=0.001；外周F=8.389,P=0.001),模型组(中枢:2.08 ±0.64；外周:1.43 ±0.46)高于两对照组(对照组1:中枢1.17 ±0.42,外周0.78±0.39;对照组2:中枢1.31±0.44,外周0.79±0.37),两对照组间差异无显著性；30只大鼠自身中枢与外周Nrg1 mRNA表达量存在正相关关系(r=0.597,P=0.000)；3组间前额叶区、齿状回区及海马区Nrg1蛋白表达差异有统计学意义(F值分别是:7.275,21.50,4.619；P值分别是:0.003,0.000,0.019),模型组(分别为7.71±2.55、11.67±1.83和10.18±2.08)高于两对照组(对照组1:4.89±1.06、7.53±1.14和7.10±2.52；对照组2:5.31±1.39、8.10±1.60和7.81±2.50),两对照组间差异无显著性.结论 MK801可以影响Nrg1基因表达变化,MK801精神分裂症动物模型Nrg1基因mRNA和蛋白表达水平升高,中枢与外周表达存在一致性改变.

Expression analysis of neuregulin 1 gene in schizophrenia model rats

Objective To analyze the gene expression of neuregulin1 (Nrg1)mRNA and protein in encephalic region and peripheral blood,and to explore the consistency of the expression in central and peripheral in schizophrenia model rat induced by dizocilpine maleate ( MK801 ).Methods 30 adult male SD rats were randomly divided into 3 groups ( 10 cases per group):model group injected with MK801 (0.6 mg/kg and 100μl/20 g)on the right rear of ventrolateral compartment,control group 1 ( no treatment) and control group 2 injected with equal volume normal saline.Nrg1 mRNA was measured in peripheral blood and in prefrontal lobe by using semiquantitative RT-PCR in 3 groups,and Nrg1 protein was measured in encephalic region (prefrontal lobe,dentate band and hippocamp) by using immunohistochemistry.Results There was significant difference of the amount of Nrg1 mRNA among 3 groups (for center:F=9.141,P =0.001 ;for peripheral blood F =8.389,P =0.001 ),and it was higher in model group ( center:2.08 ± 0.64; peripheral blood:1.43 ± 0.46) than that in two control groups ( control group1,center:1.17 ± 0.42,peripheral blood:0.78 ± 0.39 ; control group 2,center:1.31 ± 0.44,peripheral blood:0.79 ± 0.37 ),but no statistical significant difference existed between two control groups.There was positive correlation of Nrg1 mRNA between center and periphery.There was significant difference of Nrg1 protein in prefrontal lobe,dentate band and hippocamp among 3 groups ( F value was 7.275,21.50 and 4.619,and P value was 0.003,0.000 and 0.019,respectively),and it was higher in model( 7.71 ± 2.55,11.67 ± 1.83and 10.18 ±2.08,respectively)than that in two control groups( control group 1:4.89 ± 1.06,7.53 ± 1.14 and 7.10 ± 2.52,respectively; control group 2:5.31 ± 1.39,8.10 ± 1.60 and 7.81 ± 2.50),but no statistical significant difference existed between two control groups.Conclusion MK801 can effect on the expression of Nrg1 gene,Nrg1 mRNA and protein increase in MK801 model rat,and the change is synchronous between center and periphery.