诱导调节性T细胞抑制缺血性脑卒中神经炎症的研究  

Therapeutic Study on The Inhibition of Neuroinflammation in Ischemic Stroke by Induced Regulatory T Cells

作　　者：亢天放 马爱青 陈丽琦 龚含 欧阳佳城 潘璠 潘宏[1,2] 蔡林涛 KANG Tian-Fang;MA Ai-Qing;CHEN Li-Qi;GONG Han;OUYANG Jia-Cheng;PAN Fan;PAN Hong;CAI Lin-Tao(Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China;University of Chinese Academy of Sciences,Beijing 100049,China;Pharmacy School,Guangdong Medical University,Dongguan 523808,China)

机构地区：[1]中国科学院深圳先进技术研究院,深圳518055 [2]中国科学院大学,北京100049 [3]广东医科大学药学院,东莞523808

出　　处：《生物化学与生物物理进展》2025年第4期946-956,共11页Progress In Biochemistry and Biophysics

基　　金：国家重点研发计划(2022YFC2402400,2023YFA0915400);广东省自然科学基金(2024A1515010825,2022A1515011337);广东省基础与应用基础研究基金(2022A1515111168);深圳市医学科研基金(A2303057)资助项目。

摘　　要：目的神经炎症在缺血性脑卒中的发生和发展过程中起着至关重要的作用,并显著影响中枢神经系统的恢复。过度的神经炎症可能导致继发性神经元损伤,进一步加重脑损害并阻碍功能恢复。因此,有效调控和减少脑内神经炎症已成为改善缺血性脑卒中预后的关键治疗策略。在众多方法中,通过免疫调节控制炎症反应逐渐受到广泛关注。本研究旨在探讨体外诱导的调节性T细胞(Treg细胞)在抑制缺血性脑卒中后神经炎症中的作用及其潜在的治疗效果。通过研究Treg细胞发挥免疫调节功能的机制,希望为缺血性脑卒中的治疗策略提供新的科学依据。方法采用阴性选择的方法从小鼠脾脏中分离初始CD4+T细胞,以确保高纯度,然后通过添加特定细胞因子在体外诱导其分化为Treg细胞。评估Treg细胞移植在缺血性脑卒中小鼠模型中的抗炎作用及治疗潜力。在大脑中动脉闭塞(MCAO)模型中,移植Treg细胞后,观察其是否能顺利到达脑梗死区域,以及对神经炎症水平的影响。分析细胞因子表达的变化及其对免疫细胞相互作用的影响。测定梗死面积及行为学评分,以评估Treg细胞在神经保护方面的效果。通过整合多种指标,全面探讨Treg细胞在缺血性脑卒中治疗中的潜在优势。结果Treg细胞在体外和体内均显著调节了促炎和抗炎因子的表达水平,有效平衡免疫反应并抑制过度炎症。此外,Treg细胞能够抑制炎症细胞的激活和活性,从而减少神经炎症。在MCAO小鼠模型中,观察到Treg细胞在脑梗死区域富集,显著降低了梗死面积,显示出其神经保护作用。此外,Treg细胞治疗显著改善了行为学评分,提示其对功能恢复的促进作用,并且提高了缺血性脑卒中小鼠的存活率,突出了其作为卒中治疗潜在策略的应用价值。结论体外诱导的Treg细胞能够有效抑制缺血性脑卒中引发的神经炎症,展现出良好的临床Objective Neuroinflammation plays a crucial role in both the onset and progression of ischemic stroke,exerting a significant impact on the recovery of the central nervous system.Excessive neuroinflammation can lead to secondary neuronal damage,further exacerbating brain injury and impairing functional recovery.As a result,effectively modulating and reducing neuroinflammation in the brain has become a key therapeutic strategy for improving outcomes in ischemic stroke patients.Among various approaches,targeting immune regulation to control inflammation has gained increasing attention.This study aims to investigate the role of in vitro induced regulatory T cells(Treg cells)in suppressing neuroinflammation after ischemic stroke,as well as their potential therapeutic effects.By exploring the mechanisms through which Tregs exert their immunomodulatory functions,this research is expected to provide new insights into stroke treatment strategies.Methods Naive CD4+T cells were isolated from mouse spleens using a negative selection method to ensure high purity,and then they were induced in vitro to differentiate into Treg cells by adding specific cytokines.The anti-inflammatory effects and therapeutic potential of Treg cells transplantation in a mouse model of ischemic stroke was evaluated.In the middle cerebral artery occlusion(MCAO)model,after Treg cells transplantation,their ability to successfully migrate to the infarcted brain region and their impact on neuroinflammation levels were examined.To further investigate the role of Treg cells in stroke recovery,the changes in cytokine expression and their effects on immune cell interactions was analyzed.Additionally,infarct size and behavioral scores were measured to assess the neuroprotective effects of Treg cells.By integrating multiple indicators,the comprehensive evaluation of potential benefits of Treg cells in the treatment of ischemic stroke was performed.Results Treg cells significantly regulated the expression levels of both pro-inflammatory and anti-inflammatory cy

关 键 词：调节性T细胞 缺血性脑卒中 神经炎症 细胞治疗 免疫调控 

分 类 号：Q813.5[生物学—生物工程] Q819[医药卫生—神经病学与精神病学] R743.31[医药卫生—临床医学]