海南医科大学学报

目的：探讨CUMS结合CRS对小鼠海马神经胶质细胞及突触可塑性相关蛋白的影响。方法：将40只小鼠随机分为正常组（n=20）、模型组（n=20）。模型组采用CUMS结合CRS的方法制备抑郁症小鼠模型，持续造模7周。采用糖水偏好实验、旷场实验及悬尾实验对造模3周、7周末小鼠进行行为学评估；实验结束后取材，酶联免疫吸附法检测小鼠海马TNF-a的含量；免疫组化法检测小鼠海马CA1区、CA3区、DG区Iba-1、GFAP MOD值；蛋白免疫印迹法检测海马Iba-1、GFAP、SYN1、PSD-95的表达；荧光定量PCR法检测海马SYN1、PSD-95 mRNA的表达。结果：造模3周末，模型组小鼠体质量、糖水偏好率、移动总距离、直立次数、中央区停留时间均低于正常组（P<0.05），悬尾不动时间长于正常组（P<0.01）；造模7周后，模型组小鼠体质量、糖水偏好率、移动总距离、直立次数、中央区停留时间、平均运动速度均低于正常组（P<0.05），悬尾不动时间均长于正常组（P<0.01）；海马TNF-a含量高于正常组（P<0.05）；海马CA1、CA3、DG区GFAP MOD值及GFAP蛋白相对表达量均低于正常组（P<0.05）；海马CA1、CA3、DG区Iba-1 MOD值及Iba-1蛋白相对表达量均高于正常组（P<0.05）；海马SYN1、PSD-95蛋白相对表达量及SYN1、PSD-95mRNA相对表达量均低于正常组（P<0.05）。结论：经过CUMS结合CRS方法造模3周后，小鼠即可出现抑郁样行为，在造模7周后，小鼠的抑郁表现更明显。通过CUMS结合CRS方法制备的抑郁症小鼠模型可能与小鼠海马炎症水平升高，小胶质细胞过度活化、星形胶质细胞数量减少及突触可塑性下降有关。

Objective:To explore the effects of CUMS combined with CRS on mouse hippocampal glial cells and synaptic plasticity-related proteins.Methods: Forty mice were randomly divided into normal group(n=20) and model group(n=20). The model group used CUMS combined with CRS to prepare a mouse model of depression for 7 weeks. The behavioral evaluation of the mice at 3 weeks and 7 weeks after modeling was performed by sugar water preference test, open field test and tail suspension test. After the experiment, the samples were collected, and the content of TNF-a in the hippocampus of mice was detected by enzyme-linked immunosorbent assay. Immunohistochemical method was used to detect the Iba-1 and GFAP MOD values of mouse hippocampal CA1 area, CA3 area and DG area. Western blot was used to detect the protein expression of Iba-1, GFAP, SYN1and PSD-95 in the hippocampus. fluorescence quantitative PCR method was used to detect the expression of SYN1, PSD-95mRNA in hippocampus.Results: At the 3rd week after modeling, the body weight, sugar water preference rate, total distance moved, number of standing uprights, and stay time in the central area of the mice in the model group were all lower than those in the normal group(P<0.05), and the tail suspension immobility time was longer than that in the normal group(P<0.01). After 7weeks of modeling, the body weight, sugar water preference rate, total distance moved, number of erection times, central area residence time, and average movement speed of the mice in the model group were lower than those in the normal group(P<0.05), the tail suspension immobility time was longer than that in the normal group(P<0.01). The contents of TNF-a in the hippocampus were higher than those in the normal group(P<0.05). The GFAP MOD value and the relative expression of GFAP protein in hippocampal CA1, CA3 and DG regions were significantly lower than those in the normal group(P<0.05). The Iba-1MOD value and the relative expression of Iba-1 protein in hippocampal CA1, CA3 and DG regions were significantly higher than those in the normal group(P<0.05). The relative expression of SYN1 and PSD-95 protein and the relative expression of SYN1and PSD-95 mRNA in the hippocampus were significantly lower than those in the normal group(P<0.05).Conclusion: After 3weeks of CUMS and CRS modeling, the depression-like behavior of mice appeared, and the depression of mice was more obvious after 7 weeks of modeling. The depression mouse model made by CUMS combined with CRS method may be related to increased hippocampal inflammation, excessive activation of microglia, decreased number of astrocytes and decreased synaptic plasticity.objective: To explore the effects of CUMS combined with CRS on mouse hippocampal glial cells and synaptic plasticity-related proteins.