人脐带间充质干细胞(hUC-MSCs)通过调节炎症和氧化应激在缓解缺血性脑卒中诱发的脑损伤中的神经保护作用

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Guangyang Liu, Daohui Wang, Jianru Jia, Chunhua Hao, Qinggang Ge, Liqiang Xu, Chenliang Zhang, Xin Li, Yi Mi, Herui Wang, Li Miao, Yaoyao Chen, Jingwen Zhou, Xiaodan Xu, Yongjun Liu
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引用次数: 0

摘要

中风导致的脑损伤死亡率很高,仍然是全球面临的一项重大医学挑战。近年来,利用人体脐带间充质干细胞(hUC-MSCs)在不同的成人和新生儿中风动物模型中治疗中风的研究备受关注。然而,利用脐带间充质干细胞全身给药治疗缺血性中风的研究还不够深入。在本研究中,我们进行了各种实验来探索 hUC 间充质干细胞对大鼠神经的保护作用。我们的研究结果表明,静脉注射 2 × 10^7 cells/kg 的高剂量 hUC-间充质干细胞可明显改善缺血性中风导致的脑损伤。这种改善是在诱导大鼠一过性大脑中动脉闭塞(MCAO)和随后的再灌注一天后观察到的。值得注意的是,单次给药 hUC 间充质干细胞的疗效超过了依达拉奉,即使后者连续使用三天也是如此。从机理上讲,来自 hUC-间充质干细胞的分泌因子(如 HGF、BDNF 和 TNFR1)可改善 MDA 和 T-SOD 的水平,从而调节氧化应激。特别是,TNFR1 还能改善与氧化应激相关的重要蛋白质 NQO-1 和 HO-1 的表达。更重要的是,TNFR1 通过调节血液中 IL-6 的水平,在减少炎症方面发挥了重要作用。此外,TNFR1 还能影响血脑屏障(BBB)的通透性,这一点在伊凡蓝实验和 ZO-1 蛋白表达中均有体现。这项研究突破了传统方法,为临床用药和试验提供了一种新策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Neuroprotection of Human Umbilical Cord-Derived Mesenchymal Stem Cells (hUC-MSCs) in Alleviating Ischemic Stroke-Induced Brain Injury by Regulating Inflammation and Oxidative Stress

Neuroprotection of Human Umbilical Cord-Derived Mesenchymal Stem Cells (hUC-MSCs) in Alleviating Ischemic Stroke-Induced Brain Injury by Regulating Inflammation and Oxidative Stress

Neuroprotection of Human Umbilical Cord-Derived Mesenchymal Stem Cells (hUC-MSCs) in Alleviating Ischemic Stroke-Induced Brain Injury by Regulating Inflammation and Oxidative Stress

Brain injury caused by stroke has a high rate of mortality and remains a major medical challenge worldwide. In recent years, there has been significant attention given to the use of human Umbilical cord-derived Mesenchymal Stem Cells (hUC-MSCs) for the treatment of stroke in different adult and neonate animal models of stroke. However, using hUC-MSCs by systemic administration to treat ischemic stroke has not been investigated sufficiently. In this study, we conducted various experiments to explore the neuroprotection of hUC-MSCs in rats. Our findings demonstrate that an intravenous injection of a high dose of hUC-MSCs at 2 × 10^7 cells/kg markedly ameliorated brain injury resulting from ischemic stroke. This improvement was observed one day after inducing transient middle cerebral artery occlusion (MCAO) and subsequent reperfusion in rats. Notably, the efficacy of this single administration of hUC-MSCs surpassed that of edaravone, even when the latter was used continuously over three days. Mechanistically, secretory factors derived from hUC-MSCs, such as HGF, BDNF, and TNFR1, ameliorated the levels of MDA and T-SOD to regulate oxidative stress. In particular, TNFR1 also improved the expression of NQO-1 and HO-1, important proteins associated with oxidative stress. More importantly, TNFR1 played a significant role in reducing inflammation by modulating IL-6 levels in the blood. Furthermore, TNFR1 was observed to influence the permeability of the blood–brain barrier (BBB) as demonstrated in the evan’s blue experiment and protein expression of ZO-1. This study represented a breakthrough in traditional methods and provided a novel strategy for clinical medication and trials.

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来源期刊
Neurochemical Research
Neurochemical Research 医学-神经科学
CiteScore
7.70
自引率
2.30%
发文量
320
审稿时长
6 months
期刊介绍: Neurochemical Research is devoted to the rapid publication of studies that use neurochemical methodology in research on nervous system structure and function. The journal publishes original reports of experimental and clinical research results, perceptive reviews of significant problem areas in the neurosciences, brief comments of a methodological or interpretive nature, and research summaries conducted by leading scientists whose works are not readily available in English.
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