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。

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

机构信息

Department of Rehabilitation Medicine, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, 310000, Zhejiang Province, China.

Department of Neurology, Hangzhou First People's Hospital, Hangzhou, 310006, Zhejiang Province, China.

出版信息

Immun Inflamm Dis. 2024 Oct;12(10):e70008. doi: 10.1002/iid3.70008.

DOI:10.1002/iid3.70008

PMID:39364701

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11450454/

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.

摘要

背景

脑缺血性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）后的脑组织具有保护作用，但运动对 CIRI 的预防作用及其机制尚不清楚。本研究旨在探讨运动预处理对 CIRI 的影响及其机制。

方法

制备大脑中动脉闭塞（MCAO）手术以建立 CIRI 大鼠模型。所有大鼠随机分为 MCAO 组、运动（运动预处理加 MCAO 手术）组、载体（运动预处理、MCAO 手术加脑室注射空载体）组和组织金属蛋白酶抑制剂 1 过表达（OE-TIMP1，运动预处理、MCAO 手术加脑室注射 OE-TIMP1）组。

结果

结果表明，运动预处理可抑制 MCAO 大鼠约 66.67%的神经功能缺损评分和 73.79%的 TIMP1mRNA 表达，OE-TIMP1 可部分逆转运动预处理的作用。运动预处理对 MCAO 大鼠神经元死亡状态和脑梗死面积的保护作用被 OE-TIMP1 逆转。研究还证实，运动可减弱细胞凋亡和氧化应激损伤，显著增加 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产生，明显减少 BCL2 相关 X、半胱天冬酶 3 和丙二醛在 MCAO 大鼠中的产生，而这些作用被 OE-TIMP1 部分逆转。此外，运动对 MCAO 大鼠 TIMP1、低氧诱导因子-α、血管内皮生长因子受体 2、血管内皮生长因子和神经源性巢蛋白 1 蛋白水平的抑制作用也被 OE-TIMP1 部分逆转。