人脐带间充质干细胞移植对慢性应激模型小鼠抑郁行为的改善作用

doi:10.16098/j.issn.0529-1356.2021.04.005

解剖学报 ›› 2021, Vol. 52 ›› Issue (4): 528-535.doi: 10.16098/j.issn.0529-1356.2021.04.005

人脐带间充质干细胞移植对慢性应激模型小鼠抑郁行为的改善作用

赵碧春¹ 李承罡²张玉娟¹ 杜若琛¹ 原一桐¹ 张茹鑫¹ 王春芳^1*

1.山西医科大学实验动物中心，太原 030001; 2.山西医科大学第二医院骨科，太原 030001

收稿日期:2020-10-10 修回日期:2020-11-09 出版日期:2021-08-06 发布日期:2021-08-06
通讯作者: 王春芳 E-mail:wangchunfang@sxmu.edu.cn
基金资助:
小鼠骨髓间充质干细胞与神经干细胞共培养后细胞分化方向的影响及对脊髓损伤的治疗作用;miR-31过表达对神经干细胞分化增殖促进作用的研究;基于miR-31的调控作用探讨脊髓损伤修复的分子机制;基于AKT/mTOR信号通路探究人脐带间充质干细胞对自然衰老小鼠自噬水平影响的研究;基于CYP51研究万寿菊杀菌素的抗真菌机制;miR-31介导炎性因子促进脊髓损伤修复的研究

Improving effect of human umbilical cord mesenchymal stem cell transplantation on depression behavior in chronic stress model mice

ZHAO Bi-chun¹ LI Cheng-gang² ZHANG Yu-juan¹ DU Ruo-chen¹ YUAN Yi-tong¹ ZHANG Ru-xin¹WANG Chun-fang^1*

1.Experimental Animal Center of Shanxi Medical University，Taiyuan 030001, China; 2.Department of Orthopedics,the Second Hospital of Shanxi Medical University, Taiyuan 030001, China

Received:2020-10-10 Revised:2020-11-09 Online:2021-08-06 Published:2021-08-06
Contact: WANG Chun-fang E-mail:wangchunfang@sxmu.edu.cn

摘要/Abstract

摘要：

目的探讨人脐带间充质干细胞（hUCMSCs）尾静脉移植对慢性不可预测性温和应激（CUMS）模型小鼠抑郁行为的改善作用。方法获得第3代hUCMSCs；将60只C57BL/6雄性小鼠随机分为正常组、模型组（给予生理盐水）、细胞组（移植hUCMSCs）、氟西汀（flu）给药组（给予flu），每组15只。构建6周CUMS小鼠抑郁模型；从第3周开始将hUCMSCs、生理盐水以尾静脉注射的方式移植给小鼠；从第5周开始每天给予小鼠flu灌胃；记录各组小鼠每周的体重变化；通过蔗糖偏好实验、悬尾实验、强迫游泳实验及旷场实验评估小鼠抑郁模型及治疗效果；HE染色观察海马CA1及CA3区细胞变化；透射电子显微镜检测海马CA3区突触的超微结构变化；Real-time PCR检测海马突触可塑性关键蛋白突触素（SYP）和突触后致密物95（PSD-95）的mRNA表达情况。结果 hUCMSCs可以改善因CUMS导致的小鼠体重下降；行为学实验观察到，模型组小鼠出现抑郁行为，细胞组和给药组小鼠抑郁行为得到改善；HE染色观察到，与模型组相比，细胞组和给药组小鼠海马CA1及CA3区细胞排列整齐，数量增多；透射电子显微镜观察到，与模型组相比，细胞组和给药组海马CA3区亚细胞结构突触数量更多，突触间隙更窄，突触棘密度更大；Real-time PCR检测到，细胞组和给药组比模型组SYP和PSD-95的mRNA表达更多。结论 hUCMSCs移植具有抗抑郁作用，这种作用与改善海马的突触可塑性有关。

关键词: 人脐带间充质干细胞, 抑郁, 突触可塑性, 慢性不可预测性温和应激, 实时定量聚合酶链反应, 透射电子显微术, 小鼠

Abstract:

Objective To study the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) tail vein transplantation on depressive behavior in chronic unpredictable mild stress (CUMS) model mice. Methods The third generation hUCMSCs were abtained; Sixty C57BL/6 male mice were randomly divided into the normal model group (+ normal saline), the cell group (+hUCMSCs) and the fluoxetine(flu) group (+flu), with 15 mice in each group. The depression model of CUMS mice with a 6 week duration was constructed; From the third week, hUCMSCs and normal saline were transplanted into the mice by tail vein injection, and the mice were gavaged with flu daily from the fifth week; Weight changes in each group were recorded weekly; The depression model and therapeutic effect of mice were evaluated by sucrose preference test, tail suspension test, forced swimming test and open field test; The cell changes of CA1 and CA3 region in hippocampus were observed by HE staining; Transmission electron microscopy was used to detect the changes of synapses in CA3 region of hippocampus; Real-time PCR was used to detect mRNA expressions of synaphysin (SYP) and postsynaptic density protein 95(PSD-95), which are key proteins of synptic plasticity. Results hUCMSCs improved weight decrease in depressed mice; behavioral experiments observed that the model group mice showed depressive behavior, while the cell group and the drug group mice depression were improved; HE staining showed that, compared with the model group, cells in CA1 and CA3 regions of the hippocampus of mice in the cell group and the group were arranged orderly and the number of cells increased; Transmission electron microscopy showed that compared with the model group, the number of synapses in the CA3 region of the hippocampus was more, the synaptic gap was narrower, and the density of synaptic spines was higher in the cell group and the drug group; More mRNA expressions of SYP and PSD-95 were detected by Real-time PCR in the cell group and the drug group than in the model group. Conclusion hUCMSCs transplatation showes antidepressant effects, which are associated with improved synaptic plasticity in the hippocampus.

Key words: Human umbilical cord mesenchymal stem cell, Depression, Synaptic plasticity, Chronic unpredictable mild stress, Real-time PCR, Transmission electron microscopy, Mouse

中图分类号:

R363

赵碧春李承罡张玉娟杜若琛原一桐张茹鑫王春芳. 人脐带间充质干细胞移植对慢性应激模型小鼠抑郁行为的改善作用[J]. 解剖学报, 2021, 52(4): 528-535.

ZHAO Bi-chun LI Cheng-gang ZHANG Yu-juan DU Ruo-chen YUAN Yi-tong ZHANG Ru-xin WANG Chun-fang. Improving effect of human umbilical cord mesenchymal stem cell transplantation on depression behavior in chronic stress model mice[J]. Acta Anatomica Sinica, 2021, 52(4): 528-535.

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人脐带间充质干细胞移植对慢性应激模型小鼠抑郁行为的改善作用

Improving effect of human umbilical cord mesenchymal stem cell transplantation on depression behavior in chronic stress model mice

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