5-HMF通过调节GluR2改善线粒体功能,促进血管生成,在缺血性脑卒中中发挥干预作用

IF 2.2 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yan Zhang , Peipei Yuan , Yaxin Wei , Saifei Li , Lirui Zhao , Qingyun Ma , Yiran Huo , Xiaoke Zheng , Weisheng Feng
{"title":"5-HMF通过调节GluR2改善线粒体功能,促进血管生成,在缺血性脑卒中中发挥干预作用","authors":"Yan Zhang ,&nbsp;Peipei Yuan ,&nbsp;Yaxin Wei ,&nbsp;Saifei Li ,&nbsp;Lirui Zhao ,&nbsp;Qingyun Ma ,&nbsp;Yiran Huo ,&nbsp;Xiaoke Zheng ,&nbsp;Weisheng Feng","doi":"10.1016/j.bbrep.2025.102208","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>5-Hydroxymethyl furfural (5-HMF) is a furan compound with a molecular formula of C<sub>6</sub>H<sub>6</sub>O<sub>3</sub>. Studies have found that 5-HMF has many pharmacological effects, such as improving hemorheology, anti-inflammatory, antioxidant activity and anti-myocardial ischemia. Identifying the preventive effect of 5-HMF against ischemic stroke and its possible mechanism was the aim of this investigation.</div></div><div><h3>Methods</h3><div>The MCAO animal model was used to detect the related indexes of behavior, neurological function and mitochondrial function, and to clarify the effect of 5-HMF on ischemic stroke. The HBMECs model induced by OGD-R was intervened by 5-HMF, and the GluR2 silencing sequence was added to detect mitochondrial function and angiogenesis-related indicators, so as to further explore the mechanism of 5-HMF intervention in ischemic stroke.</div></div><div><h3>Results</h3><div>In the MCAO experiment, the behavioral results showed that 5-HMF increased the quantity of autonomic activities, increased the exercise time and distance, reduced the balance beam score, and prolonged the residence time of MCAO rats on the rotating rod (<em>P</em> &lt; 0.01). The results of neurological function indicated that 5-HMF reduced the neurological function score, increased the blood flow velocity of middle cerebral artery (<em>P</em> &lt; 0.01), reduced the area of cerebral infarction, and alleviated the damage of cerebral cortex and hippocampal neurons. The results of mitochondrial function indicated that 5-HMF could significantly reduce the apoptosis of primary brain cells, ROS, Ca<sup>2+</sup> levels, increase mitochondrial membrane potential and GluR2 expression in MCAO rats (<em>P</em> &lt; 0.01). In the OGD-R-induced HBMECs experiment, 5-HMF increased the expression level of GluR2, increased cell viability, and decreased LDH activity in cell supernatant (<em>P</em> &lt; 0.01). The results of mitochondrial function showed that 5-HMF reduced the levels of Ca<sup>2+</sup> and glutamate in the cell supernatant, reduced the levels of apoptosis and ROS, increased the mitochondrial membrane potential, and improved the expression of mitochondrial dynamics-related proteins (<em>P</em> &lt; 0.05 or <em>P</em> &lt; 0.01). These improvements were markedly reversed after the addition of GluR2 silencing sequence (<em>P</em> &lt; 0.01).</div></div><div><h3>Conclusions</h3><div>5-HMF has the effect of ameliorating brain damage in MCAO rats, and by regulating the expression of GluR2, reducing intracellular Ca<sup>2+</sup> concentration, improving mitochondrial function, promoting angiogenesis, thereby reducing OGD-R-induced HBMECs damage.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"44 ","pages":"Article 102208"},"PeriodicalIF":2.2000,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"5-HMF plays an intervention role in ischemic stroke by regulating GluR2 to improve mitochondrial function and promote angiogenesis\",\"authors\":\"Yan Zhang ,&nbsp;Peipei Yuan ,&nbsp;Yaxin Wei ,&nbsp;Saifei Li ,&nbsp;Lirui Zhao ,&nbsp;Qingyun Ma ,&nbsp;Yiran Huo ,&nbsp;Xiaoke Zheng ,&nbsp;Weisheng Feng\",\"doi\":\"10.1016/j.bbrep.2025.102208\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><div>5-Hydroxymethyl furfural (5-HMF) is a furan compound with a molecular formula of C<sub>6</sub>H<sub>6</sub>O<sub>3</sub>. Studies have found that 5-HMF has many pharmacological effects, such as improving hemorheology, anti-inflammatory, antioxidant activity and anti-myocardial ischemia. Identifying the preventive effect of 5-HMF against ischemic stroke and its possible mechanism was the aim of this investigation.</div></div><div><h3>Methods</h3><div>The MCAO animal model was used to detect the related indexes of behavior, neurological function and mitochondrial function, and to clarify the effect of 5-HMF on ischemic stroke. The HBMECs model induced by OGD-R was intervened by 5-HMF, and the GluR2 silencing sequence was added to detect mitochondrial function and angiogenesis-related indicators, so as to further explore the mechanism of 5-HMF intervention in ischemic stroke.</div></div><div><h3>Results</h3><div>In the MCAO experiment, the behavioral results showed that 5-HMF increased the quantity of autonomic activities, increased the exercise time and distance, reduced the balance beam score, and prolonged the residence time of MCAO rats on the rotating rod (<em>P</em> &lt; 0.01). The results of neurological function indicated that 5-HMF reduced the neurological function score, increased the blood flow velocity of middle cerebral artery (<em>P</em> &lt; 0.01), reduced the area of cerebral infarction, and alleviated the damage of cerebral cortex and hippocampal neurons. The results of mitochondrial function indicated that 5-HMF could significantly reduce the apoptosis of primary brain cells, ROS, Ca<sup>2+</sup> levels, increase mitochondrial membrane potential and GluR2 expression in MCAO rats (<em>P</em> &lt; 0.01). In the OGD-R-induced HBMECs experiment, 5-HMF increased the expression level of GluR2, increased cell viability, and decreased LDH activity in cell supernatant (<em>P</em> &lt; 0.01). The results of mitochondrial function showed that 5-HMF reduced the levels of Ca<sup>2+</sup> and glutamate in the cell supernatant, reduced the levels of apoptosis and ROS, increased the mitochondrial membrane potential, and improved the expression of mitochondrial dynamics-related proteins (<em>P</em> &lt; 0.05 or <em>P</em> &lt; 0.01). These improvements were markedly reversed after the addition of GluR2 silencing sequence (<em>P</em> &lt; 0.01).</div></div><div><h3>Conclusions</h3><div>5-HMF has the effect of ameliorating brain damage in MCAO rats, and by regulating the expression of GluR2, reducing intracellular Ca<sup>2+</sup> concentration, improving mitochondrial function, promoting angiogenesis, thereby reducing OGD-R-induced HBMECs damage.</div></div>\",\"PeriodicalId\":8771,\"journal\":{\"name\":\"Biochemistry and Biophysics Reports\",\"volume\":\"44 \",\"pages\":\"Article 102208\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-08-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemistry and Biophysics Reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S240558082500295X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemistry and Biophysics Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S240558082500295X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

5-羟甲基糠醛(5-HMF)是分子式为C6H6O3的呋喃类化合物。研究发现5-HMF具有改善血液流变学、抗炎、抗氧化、抗心肌缺血等药理作用。确定5-羟甲基糠醛对缺血性脑卒中的预防作用及其可能的机制是本研究的目的。方法采用MCAO动物模型检测大鼠行为、神经功能、线粒体功能等相关指标,明确5-HMF对缺血性脑卒中的影响。通过5-HMF干预OGD-R诱导的hbmec模型,加入GluR2沉默序列检测线粒体功能和血管生成相关指标,进一步探讨5-HMF干预缺血性脑卒中的机制。结果在MCAO实验中,行为学结果显示,5-HMF增加了MCAO大鼠的自主活动量,增加了运动时间和距离,降低了平衡木评分,延长了MCAO大鼠在旋转杆上的停留时间(P < 0.01)。神经功能结果显示,5-HMF降低大鼠神经功能评分,增加大脑中动脉血流速度(P < 0.01),缩小脑梗死面积,减轻大脑皮层和海马神经元损伤。线粒体功能结果显示,5-HMF能显著降低MCAO大鼠原代脑细胞凋亡、ROS、Ca2+水平,提高线粒体膜电位和GluR2表达(P < 0.01)。在ogd - r诱导的HBMECs实验中,5-HMF提高了GluR2的表达水平,提高了细胞活力,降低了细胞上清LDH活性(P < 0.01)。线粒体功能结果显示,5-HMF降低细胞上清中Ca2+和谷氨酸水平,降低细胞凋亡和ROS水平,增加线粒体膜电位,改善线粒体动力学相关蛋白的表达(P <; 0.05或P <; 0.01)。添加GluR2沉默序列后,这些改善明显逆转(P < 0.01)。结论5- hmf具有改善MCAO大鼠脑损伤的作用,通过调节GluR2的表达,降低细胞内Ca2+浓度,改善线粒体功能,促进血管生成,从而减轻ogd - r诱导的hbmec损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
5-HMF plays an intervention role in ischemic stroke by regulating GluR2 to improve mitochondrial function and promote angiogenesis

Introduction

5-Hydroxymethyl furfural (5-HMF) is a furan compound with a molecular formula of C6H6O3. Studies have found that 5-HMF has many pharmacological effects, such as improving hemorheology, anti-inflammatory, antioxidant activity and anti-myocardial ischemia. Identifying the preventive effect of 5-HMF against ischemic stroke and its possible mechanism was the aim of this investigation.

Methods

The MCAO animal model was used to detect the related indexes of behavior, neurological function and mitochondrial function, and to clarify the effect of 5-HMF on ischemic stroke. The HBMECs model induced by OGD-R was intervened by 5-HMF, and the GluR2 silencing sequence was added to detect mitochondrial function and angiogenesis-related indicators, so as to further explore the mechanism of 5-HMF intervention in ischemic stroke.

Results

In the MCAO experiment, the behavioral results showed that 5-HMF increased the quantity of autonomic activities, increased the exercise time and distance, reduced the balance beam score, and prolonged the residence time of MCAO rats on the rotating rod (P < 0.01). The results of neurological function indicated that 5-HMF reduced the neurological function score, increased the blood flow velocity of middle cerebral artery (P < 0.01), reduced the area of cerebral infarction, and alleviated the damage of cerebral cortex and hippocampal neurons. The results of mitochondrial function indicated that 5-HMF could significantly reduce the apoptosis of primary brain cells, ROS, Ca2+ levels, increase mitochondrial membrane potential and GluR2 expression in MCAO rats (P < 0.01). In the OGD-R-induced HBMECs experiment, 5-HMF increased the expression level of GluR2, increased cell viability, and decreased LDH activity in cell supernatant (P < 0.01). The results of mitochondrial function showed that 5-HMF reduced the levels of Ca2+ and glutamate in the cell supernatant, reduced the levels of apoptosis and ROS, increased the mitochondrial membrane potential, and improved the expression of mitochondrial dynamics-related proteins (P < 0.05 or P < 0.01). These improvements were markedly reversed after the addition of GluR2 silencing sequence (P < 0.01).

Conclusions

5-HMF has the effect of ameliorating brain damage in MCAO rats, and by regulating the expression of GluR2, reducing intracellular Ca2+ concentration, improving mitochondrial function, promoting angiogenesis, thereby reducing OGD-R-induced HBMECs damage.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics
CiteScore
4.60
自引率
0.00%
发文量
191
审稿时长
59 days
期刊介绍: Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信