骨髓间充质干细胞缓解模拟微重力对小鼠大脑皮质的不利影响

doi:10.16352/j.issn.1001-6325.2024.06.0772

基础医学与临床 ›› 2024, Vol. 44 ›› Issue (6): 772-778.doi: 10.16352/j.issn.1001-6325.2024.06.0772

骨髓间充质干细胞缓解模拟微重力对小鼠大脑皮质的不利影响

龚金涛¹, 厉建伟², 李玉恒², 李堑¹, 赵春华^1*

1.中国医学科学院基础医学研究所北京协和医学院基础学院组织工程中心, 北京 100005;
2.中国航天员科研训练中心航天医学全国重点实验室, 北京 100094

收稿日期:2024-02-18 修回日期:2024-04-24 出版日期:2024-06-05 发布日期:2024-05-24
通讯作者: ^*zhaochunhua@ibms.pumc.edu.cn
基金资助:
中国医学科学院医学与健康科技创新工程(2022-I2M-1-012);全国重点实验室专项经费(2060204);国家重点研发计划(2020YFA0113000);高等学校学科创新引智计划(B18007)

Bone marrow-derived mesenchymal stem cells relieve the adverse effects of simulated microgravity on mouse cerebral cortex

GONG Jintao¹, LI Jianwei², LI Yuheng², LI Qian¹, ZHAO Chunhua^1*

1. Center for Excellence in Tissue Engineering, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005;
2. State Key Laboratory of Space Medicine Fundamentals and Application, China Astronaut Research and Training Center, Beijing 100094, China

Received:2024-02-18 Revised:2024-04-24 Online:2024-06-05 Published:2024-05-24
Contact: ^*zhaochunhua@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的探究骨髓间充质干细胞(BMSCs)对微重力环境下大脑的保护和分子调节机制。方法以后肢去负荷 (HU)模型模拟失重生理效应,将小鼠分为:对照组,HU模型组、BMSCs治疗组,每组6只,对比分析模拟微重力对小鼠大脑造成的损伤及BMSCs对损伤的修复作用;利用RT-qPCR检测大脑皮质中关键促炎因子Il-6、Il-1β和Tnf-α的表达水平;利用免疫组织化学染色检测大脑皮质中小胶质细胞(IBA1阳性)和星形胶质细胞(GFAP阳性)的比例;利用Western blot 检测细胞凋亡与衰老相关蛋白BAX、BCL-2、p21、p53的表达水平。结果与野生小鼠相比,后肢去负荷小鼠大脑皮质的Il-6、Il-1β和Tnf-α的表达水平显著上升(P＜0.05),BAX、p21和p53蛋白的表达水平显著升高(P＜0.05),BCL-2蛋白的表达水平显著降低(P＜0.05),小胶质细胞(IBA1阳性)和星形胶质细胞(GFAP阳性)的比例升高(P＜0.05); 经过BMSCs治疗以后,HU小鼠大脑皮质的Il-1β的表达水平显著降低(P＜0.05),BAX、p21和p53蛋白的表达水平显著降低(P＜0.05),BCL-2蛋白的表达水平显著升高(P＜0.05),小胶质细胞(IBA1阳性)和星形胶质细胞(GFAP阳性)的比例减少(P＜0.05)。结论 BMSCs通过抑制炎性反应、抗细胞凋亡与衰老来缓解模拟失重对小鼠大脑产生的不利影响。

关键词: 间充质干细胞(MSCs), 微重力, 后肢去负荷, 凋亡, 细胞衰老

Abstract: Objective To explore the protective effects and the underlying mechanisms of bone marrow mesenchymal stem cells (BMSCs) on the brain in microgravity environment. Methods The physiological effects of microgravity were simulated with the hindlimb unloading (HU) mouse model. The animals were divided into 3 groups: the control group (wild-type mice), the hindlimb unloading (HU) group, and the BMSCs treatment group, with six in each. RT-qPCR was adopted to determine the expression levels of pro-inflammatory cytokines (Il-6, Il-1β and Tnf-α) in the cerebral cortex; immunohistochemistry was performed to evaluate the proportions of microglia (IBA-positive) and astrocytes (GFAP-positive); Western blot was used to measure the expression levels of apoptosis-and senescence-related molecules (BAX, BCL-2, p21, and p53). Results Compared with wild-type mice, the expression levels of Il-6, Il-1β and Tnf-α in the cerebral cortex of HU mice were significantly increased (P＜0.05), the expression level of BAX, p21 and p53 was also significantly increased(P＜0.05). However, the expression level of BCL-2 protein were significantly decreased (P＜0.05). The proportion of microglia (IBA1 positive) and astrocytes (GFAP positive) was increased (P＜0.05); After BMSCs treatment, the expression level of Il-1β in the cerebral cortex of HU mice was significantly decreased (P＜0.05), the expression levels of BAX, p21 and p53 were significantly decreased (P＜0.05), and the expression level of BCL-2 protein was significantly increased (P＜0.05). The proportion of microglia (IBA1 positive) and astrocytes (GFAP positive) decreased (P＜0.05). Conclusions BMSCs potentially relieve the detrimental effects of simulated microgravity on mouse brain by inhibiting inflammation, apoptosis and cellular senescence.

Key words: mesenchymal stem cells, microgravity, hindlimb unloading, apoptosis, cellular senescence

中图分类号:

R851.22

龚金涛, 厉建伟, 李玉恒, 李堑, 赵春华. 骨髓间充质干细胞缓解模拟微重力对小鼠大脑皮质的不利影响[J]. 基础医学与临床, 2024, 44(6): 772-778.

GONG Jintao, LI Jianwei, LI Yuheng, LI Qian, ZHAO Chunhua. Bone marrow-derived mesenchymal stem cells relieve the adverse effects of simulated microgravity on mouse cerebral cortex[J]. Basic & Clinical Medicine, 2024, 44(6): 772-778.

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骨髓间充质干细胞缓解模拟微重力对小鼠大脑皮质的不利影响

Bone marrow-derived mesenchymal stem cells relieve the adverse effects of simulated microgravity on mouse cerebral cortex

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