GPR68 通过 NF-κB/Hif-1α 通路对脑缺血再灌注损伤的神经保护作用

IF 3.5 3区 医学 Q2 NEUROSCIENCES
Xianglong Li , Kaiguo Xia , Chuanhong Zhong , Xiangzhou Chen , Fubing Yang , Ligang Chen , Jian You
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引用次数: 0

摘要

背景:G蛋白偶联受体68(GPR68)是一种孤儿受体,已成为减轻神经元炎症和氧化损伤的一个有希望的治疗靶点。本研究探讨了 GPR68 在脑缺血再灌注损伤(CIRI)中的保护机制:方法:建立了体内大脑中动脉闭塞/再灌注(MCAO/R)小鼠模型。小鼠腹腔注射选择性 GPR68 激动剂 Ogerin。采用实时定量聚合酶链反应(RT-qPCR)、酶联免疫吸附试验(ELISA)和流式细胞术评估了氧-葡萄糖剥夺/再灌注(OGD/R)对细胞活力的影响:结果:GPR68的表达在经OGD/R处理的细胞中受到抑制,而其上调则对SH-SY5Y和HMC3细胞起到保护作用。在体内,受 MCAO/R 影响的脑组织中 GPR68 的水平降低,这与氧化应激、炎症和神经损伤有关。用 GPR68 激动剂治疗可减少 MCAO/R 引起的脑梗塞、细胞凋亡和基因表达失调。从机制上讲,GPR68 激动剂治疗可能会抑制 NF-κB/Hif-1α 通路的激活,从而减少氧化和炎症反应,增强对 CIRI 的保护:本研究证实,GPR68/NF-κB/Hif-1α 轴可调节 CIRI 中的细胞凋亡、炎症和氧化应激,表明 GPR68 是 CIRI 的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Neuroprotective effects of GPR68 against cerebral ischemia-reperfusion injury via the NF-κB/Hif-1α pathway

Background

G protein-coupled receptor 68 (GPR68), an orphan receptor, has emerged as a promising therapeutic target for mitigating neuronal inflammation and oxidative damage. This study explores the protective mechanisms of GPR68 in cerebral ischemia-reperfusion injury (CIRI).

Methods

An in vivo middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model was established. Mice received intraperitoneal injections of Ogerin, a selective GPR68 agonist. In vitro, GPR68 was overexpressed in SH-SY5Y and HMC3 cells, and the effects of oxygen-glucose deprivation/reperfusion (OGD/R) on cell viability were assessed using real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry.

Results

The expression of GPR68 was suppressed in cells subjected to OGD/R treatment, whereas its upregulation conferred protection to SH-SY5Y and HMC3 cells. In vivo, levels of GPR68 were reduced in brain tissues affected by MCAO/R, correlating with oxidative stress, inflammation, and neurological damage. Treatment with a GPR68 agonist decreased brain infarction, apoptosis, and dysregulated gene expression induced by MCAO/R. Mechanistically, GPR68 agonist treatment may inhibit the activation of the NF-κB/Hif-1α pathway, thereby reducing oxidative and inflammatory responses and enhancing protection against CIRI.

Conclusions

This study confirms that the GPR68/NF-κB/Hif-1α axis modulates apoptosis, inflammation, and oxidative stress in CIRI, indicating that GPR68 is a potential therapeutic target for CIRI.

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来源期刊
Brain Research Bulletin
Brain Research Bulletin 医学-神经科学
CiteScore
6.90
自引率
2.60%
发文量
253
审稿时长
67 days
期刊介绍: The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.
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