Exercise preconditioning mitigates brain injury after cerebral ischemia-reperfusion injury in rats by restraining TIMP1.

IF 3.1 4区 医学 Q3 IMMUNOLOGY
Xiangbo Meng, Hui Yang, Feifeng Chen, Baohua Li, Yan Wu, Rong Wang
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Abstract

Background: Cerebral ischemic disease is a common cerebrovascular disease, especially ischemic stroke. Exercise has protective functions on brain tissues following cerebral ischemia-reperfusion injury (CIRI), but its preventive effects and mechanisms in CIRI remain unclear. We aimed to investigate the effects and mechanisms of exercise preconditioning on CIRI.

Methods: The middle cerebral artery occlusion (MCAO) operation was prepared to establish CIRI rats. All rats were randomized into the MCAO, exercise (exercise preconditioning plus MCAO operation), vector (exercise preconditioning, MCAO operation plus intraventricular injection of empty vector), and tissue inhibitor of metalloprotease 1 overexpression (OE-TIMP1, exercise preconditioning, MCAO operation plus intraventricular injection of OE-TIMP1) groups.

Results: The results indicated that exercise preconditioning suppressed approximately 66.67% of neurological deficit scores and 73.79% of TIMP1 mRNA expression in MCAO rats, which were partially offset by OE-TIMP1. The protective effects of exercise against neuron death status and cerebral infarction size in MCAO rats were reversed by OE-TIMP1. It also confirmed that exercise weakened apoptosis and oxidative stress damage, with notable increases of B-cell lymphoma-2, superoxide dismutase, and glutathione peroxidase production, and evident decreases of BCL2-associated X, caspase 3, and malondialdehyde in MCAO rats, while these effects were partially reversed by OE-TIMP1. Additionally, the inhibitory effects of exercise on the protein levels of TIMP1, hypoxia-inducible factor-alpha, vascular endothelial growth factor receptor 2, vascular endothelial growth factor, and neurogenic locus notch homolog protein 1 in MCAO rats were partially reversed by OE-TIMP1.

Conclusion: Altogether, exercise preconditioning had protective effects on CIRI by restraining TIMP1, which provided new therapeutic strategies for preventing CIRI.

运动预处理通过抑制 TIMP1 减轻大鼠脑缺血再灌注损伤后的脑损伤
背景:脑缺血疾病是一种常见的脑血管疾病,尤其是缺血性脑卒中。运动对脑缺血再灌注损伤(CIRI)后的脑组织有保护作用,但其对CIRI的预防作用和机制尚不清楚。我们旨在研究运动预处理对 CIRI 的影响和机制:方法:准备大脑中动脉闭塞(MCAO)手术,建立 CIRI 大鼠。所有大鼠随机分为MCAO组、运动组(运动预处理加MCAO手术)、载体组(运动预处理、MCAO手术加脑室内注射空载体)和组织金属蛋白酶1抑制剂过表达组(OE-TIMP1、运动预处理、MCAO手术加脑室内注射OE-TIMP1):结果表明,运动预处理抑制了 MCAO 大鼠约 66.67% 的神经功能缺损评分和 73.79% 的 TIMP1 mRNA 表达,而 OE-TIMP1 则部分抵消了这一作用。运动对 MCAO 大鼠神经元死亡状态和脑梗塞面积的保护作用被 OE-TIMP1 逆转。研究还证实,运动削弱了 MCAO 大鼠的细胞凋亡和氧化应激损伤,B 细胞淋巴瘤-2、超氧化物歧化酶和谷胱甘肽过氧化物酶的生成明显增加,BCL2 相关 X、Caspase 3 和丙二醛的生成明显减少,而这些效应被 OE-TIMP1 部分逆转。此外,OE-TIMP1 还能部分逆转运动对 MCAO 大鼠体内 TIMP1、缺氧诱导因子-α、血管内皮生长因子受体 2、血管内皮生长因子和神经原位点缺口同源蛋白 1 蛋白水平的抑制作用:总之,运动预处理通过抑制 TIMP1 对 CIRI 具有保护作用,为预防 CIRI 提供了新的治疗策略。
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来源期刊
Immunity, Inflammation and Disease
Immunity, Inflammation and Disease Medicine-Immunology and Allergy
CiteScore
3.60
自引率
0.00%
发文量
146
审稿时长
8 weeks
期刊介绍: Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology
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