慢性不可预见性应激模型大鼠海马形态及其糖皮质激素受体表达的动态观察

［摘要］目的: 观察慢性不可预见性刺激（chronic unpredictable mild stress,CUMS）所致抑郁症模型大鼠海马形态和神经元糖皮质激素受体（glucocorticoid receptor,GR）的表达变化。方法: 用CUMS法刺激大鼠建立抑郁模型。取CUMS后2周，4周，6周大鼠海马组织，以未经刺激的大鼠海马组织为对照组，利用免疫荧光技术以及RT PCR方法分别检测各组大鼠海马神经元GR表达的分布和GR mRNA的表达；采用MRI和HE染色观察海马形态结构。结果： 激光共聚焦显微镜下，对照组可见海马CA1区、CA3区及齿状回区细胞GR表达丰富，荧光强度较高，表达GR的细胞排列紧密有序，形态饱满。与对照组比较，随着应激时间的增加，模型组大鼠海马各区GR的荧光表达强度依次减弱，GR阳性细胞数量减少，形态趋向紊乱。GR免疫反应细胞计数显示模型组海马GR阳性细胞数量明显低于对照组(P<0.01)。RT PCR显示模型组海马组织GR mRNA表达较对照组明显降低(P<0.01)。与对照组比较，模型组大鼠海马形态发生显著变化，随着刺激时间的延长，2周，4周，6周模型组大鼠海马细胞排列逐渐紊乱，细胞数量逐渐减少，形态不规则。结论： CUMS抑郁模型大鼠海马神经元内GR表达明显减少，此可能为大鼠海马神经元受损的机制之一。

Dynamic change of the expression of glucocorticoid receptor in the hippocampus of rat model of depression by chronic unpredictable mild stress

［Abstract］Objective To explore the change of the expression of glucocorticoid receptor(GR) in the hippocampus of rat model of depression by chronic unpredictable mild stress(CUMS). MethodsA rat model of depression was established with CUMS method.The rat hippocampus tissues at week 2 and 4 and 6 after CUMS were extracted and the normal hippocampus tissues used as control were collected.The expressions of GR in the hippocampus in each group were observed by the immunofluorescent staining,and RT-PCR method was applied to measure the expression of GR mRNA in hippocampus.Using MRI and HE staining method was used to analyze the morphological and structural changes of hippocampus of each group. ResultsGR was expressed in abundance in control group and fluorescence intensity was high.The expressive cell arranged closely and regularly. Compared with the control group,as the stress going on, the fluorescence intensity of GR expression in depressive hippocampus gradually weakened and the number of GR expression cell gradually fell, the morphological of hippocampus cell had become disorder. GR-positive cell number was significant lower than control group(P<0.01).The expression of GR mRNA in the depressive group was significantly reduced compared to the control group(P<0.01).The morphological and structural changes of hippocampus had the significant change in the depressive group. The hippocampus cells of rats at week 2 and 4 and 6 after stress were arranged disorderly and the count decreased,the morphological and structural had become irregular. ConclusionThe decrease of GR in the hippocampus of rat model of depression by CUMS may be one of the underlying mechanisms to explain the occurrence of hippocampal neurons damage.