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ISO-1 抑制细胞凋亡通过线粒体通路对缺血性中风的保护作用。

Ischemic stroke protected by ISO-1 inhibition of apoptosis via mitochondrial pathway.

机构信息

Department of Neurology II, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, 88 Jiankang Road, Weihui, Xinxiang, 453100, Henan, China.

Henan Key Laboratory of Neural Regeneration, Weihui, Xinxiang, 453100, China.

出版信息

Sci Rep. 2023 Feb 16;13(1):2788. doi: 10.1038/s41598-023-29907-z.

DOI:10.1038/s41598-023-29907-z
PMID:36797398
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9935850/
Abstract

Macrophage migration inhibitory factor (MIF) is an immune mediator associated with inflammation, which is upregulated after ischemia in brain tissue. ISO-1 is a potent inhibitor of MIF tautomerase and can protect neurons by reducing the permeability of blood brain barrier (BBB). In this study, we investigated the role of ISO-1 in cerebral ischemia/reperfusion injury by establishing a model of middle cerebral artery occlusion/reperfusion in rats. Rats were randomly divided into four groups: the sham operation group, the ISO-1group, the cerebral I/R group, and the ISO-1 + I/R group. We assessed the degree of neurological deficit in each group and measured the volume of cerebral infarction. We detected the expression of MIF in the core necrotic area and penumbra. We detected the expression of apoptosis-related proteins, apoptosis-inducing factor (AIF), endonuclease G (EndoG) and cytochrome c oxidase-IV (COX-IV) in the ischemic penumbra region. The results showed that MIF was expressed in the ischemic penumbra, while the injection of ISO-1 was able to alleviate neurological damage and reduce the infarction volume. In the cerebral ischemic penumbra region, ISO-1 could reduce the expression of Bax and Caspase3 and inhibit the displacement of AIF and EndoG to the nucleus simultaneously. Besides, ISO-1 also exhibited the ability to reduce apoptosis. In summary, ISO-1 may inhibit neuronal apoptosis through the endogenous mitochondrial pathway and reduce the injury of brain I/R after ischemic stroke.

摘要

巨噬细胞移动抑制因子（MIF）是一种与炎症相关的免疫介质，在脑组织缺血后上调。ISO-1 是 MIF 互变异构酶的有效抑制剂，通过降低血脑屏障（BBB）的通透性来保护神经元。在这项研究中，我们通过建立大鼠大脑中动脉闭塞/再灌注模型，研究了 ISO-1 在脑缺血/再灌注损伤中的作用。大鼠随机分为四组：假手术组、ISO-1 组、脑 I/R 组和 ISO-1+I/R 组。我们评估了每组的神经功能缺损程度，并测量了脑梗死体积。我们检测了核心坏死区和半影区 MIF 的表达。我们检测了缺血半影区凋亡相关蛋白、凋亡诱导因子（AIF）、核酸内切酶 G（EndoG）和细胞色素 c 氧化酶-IV（COX-IV）的表达。结果表明，MIF 在缺血半影区表达，而 ISO-1 的注射能够减轻神经损伤并减少梗死体积。在脑缺血半影区，ISO-1 可以降低 Bax 和 Caspase3 的表达，并同时抑制 AIF 和 EndoG 向核内的移位。此外，ISO-1 还具有抑制细胞凋亡的能力。综上所述，ISO-1 可能通过内源性线粒体途径抑制神经元凋亡，减轻缺血性脑卒中后脑 I/R 的损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/9935850/e8f1f5c9242b/41598_2023_29907_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/9935850/e8f1f5c9242b/41598_2023_29907_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a1e1/9935850/4ae074e5cb80/41598_2023_29907_Fig1_HTML.jpg
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