• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

缺氧缺血后给予二甲双胍治疗可减轻新生大鼠的脑损伤。

Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats.

作者信息

Fang Mingchu, Jiang Huai, Ye Lixia, Cai Chenchen, Hu Yingying, Pan Shulin, Li Peijun, Xiao Jian, Lin Zhenlang

机构信息

Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China.

Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, United States.

出版信息

Oncotarget. 2017 Sep 8;8(43):75308-75325. doi: 10.18632/oncotarget.20779. eCollection 2017 Sep 26.

DOI:10.18632/oncotarget.20779
PMID:29088867
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5650422/
Abstract

Neonatal hypoxic-ischemic (HI) brain injury is a devastating disease that often leads to death and detrimental neurological deficits. The present study was designed to evaluate the ability of metformin to provide neuroprotection in a model of neonatal hypoxic-ischemic brain injury and to study the associated molecular mechanisms behind these protective effects. Here, we found that metformin treatment remarkably attenuated brain infarct volumes and brain edema at 24 h after HI injury, and the neuroprotection of metformin was associated with inhibition of neuronal apoptosis, suppression of the neuroinflammation and amelioration of the blood brain barrier breakdown. Additionally, metformin treatment conferred long-term protective against brain damage at 7 d after HI injury. Our study indicates that metformin treatment protects against neonatal hypoxic-ischemic brain injury and thus has potential as a therapy for this disease.

摘要

新生儿缺氧缺血性脑损伤是一种毁灭性疾病，常导致死亡和严重的神经功能缺损。本研究旨在评估二甲双胍在新生儿缺氧缺血性脑损伤模型中提供神经保护的能力，并研究这些保护作用背后的相关分子机制。在此，我们发现二甲双胍治疗在缺氧缺血性损伤后24小时显著减轻脑梗死体积和脑水肿，且二甲双胍的神经保护作用与抑制神经元凋亡、抑制神经炎症以及改善血脑屏障破坏有关。此外，二甲双胍治疗在缺氧缺血性损伤后7天对脑损伤具有长期保护作用。我们的研究表明，二甲双胍治疗可预防新生儿缺氧缺血性脑损伤，因此具有作为该疾病治疗方法的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/5015c2a17e01/oncotarget-08-75308-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/24486e508486/oncotarget-08-75308-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/524f0e2d8674/oncotarget-08-75308-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/e3f093c398a7/oncotarget-08-75308-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/7ef0e3a3f428/oncotarget-08-75308-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/8a642ef68f6f/oncotarget-08-75308-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/f14f4409ee33/oncotarget-08-75308-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/c706c895e66b/oncotarget-08-75308-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/7516484ea252/oncotarget-08-75308-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/5015c2a17e01/oncotarget-08-75308-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/24486e508486/oncotarget-08-75308-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/524f0e2d8674/oncotarget-08-75308-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/e3f093c398a7/oncotarget-08-75308-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/7ef0e3a3f428/oncotarget-08-75308-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/8a642ef68f6f/oncotarget-08-75308-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/f14f4409ee33/oncotarget-08-75308-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/c706c895e66b/oncotarget-08-75308-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/7516484ea252/oncotarget-08-75308-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0325/5650422/5015c2a17e01/oncotarget-08-75308-g009.jpg

相似文献

1
Metformin treatment after the hypoxia-ischemia attenuates brain injury in newborn rats.缺氧缺血后给予二甲双胍治疗可减轻新生大鼠的脑损伤。
Oncotarget. 2017 Sep 8;8(43):75308-75325. doi: 10.18632/oncotarget.20779. eCollection 2017 Sep 26.
2
Protective effects of FGF10 on neurovascular unit in a rat model of neonatal hypoxic-ischemic brain injury.FGF10 对新生大鼠缺氧缺血性脑损伤模型神经血管单元的保护作用。
Exp Neurol. 2020 Oct;332:113393. doi: 10.1016/j.expneurol.2020.113393. Epub 2020 Jun 29.
3
Inhibition of microRNA-210 provides neuroprotection in hypoxic-ischemic brain injury in neonatal rats.抑制微小RNA-210对新生大鼠缺氧缺血性脑损伤具有神经保护作用。
Neurobiol Dis. 2016 May;89:202-12. doi: 10.1016/j.nbd.2016.02.011. Epub 2016 Feb 11.
4
Vitexin reduces hypoxia-ischemia neonatal brain injury by the inhibition of HIF-1alpha in a rat pup model.在幼鼠模型中，牡荆素通过抑制缺氧诱导因子-1α（HIF-1α）减轻新生儿缺氧缺血性脑损伤。
Neuropharmacology. 2015 Dec;99:38-50. doi: 10.1016/j.neuropharm.2015.07.007. Epub 2015 Jul 14.
5
Neuroprotection by selective neuronal deletion of Atg7 in neonatal brain injury.新生脑损伤中通过选择性神经元缺失Atg7实现神经保护作用。
Autophagy. 2016;12(2):410-23. doi: 10.1080/15548627.2015.1132134.
6
TRPM7 inhibitor carvacrol protects brain from neonatal hypoxic-ischemic injury.TRPM7抑制剂香芹酚可保护大脑免受新生儿缺氧缺血性损伤。
Mol Brain. 2015 Feb 19;8:11. doi: 10.1186/s13041-015-0102-5.
7
Matrix metalloproteinases inhibition provides neuroprotection against hypoxia-ischemia in the developing brain.基质金属蛋白酶抑制可为发育中的大脑提供针对缺氧缺血的神经保护作用。
J Neurochem. 2009 Nov;111(3):726-36. doi: 10.1111/j.1471-4159.2009.06362.x. Epub 2009 Aug 27.
8
Neuronal K(ATP) channels mediate hypoxic preconditioning and reduce subsequent neonatal hypoxic-ischemic brain injury.神经元ATP敏感性钾通道介导低氧预处理并减轻随后的新生儿缺氧缺血性脑损伤。
Exp Neurol. 2015 Jan;263:161-71. doi: 10.1016/j.expneurol.2014.10.003. Epub 2014 Oct 18.
9
Neuroprotective effect of the peptides ADNF-9 and NAP on hypoxic-ischemic brain injury in neonatal rats.肽ADNF-9和NAP对新生大鼠缺氧缺血性脑损伤的神经保护作用。
Brain Res. 2006 Oct 18;1115(1):169-78. doi: 10.1016/j.brainres.2006.07.114. Epub 2006 Aug 30.
10
Genetic deletion of neuronal pentraxin 1 expression prevents brain injury in a neonatal mouse model of cerebral hypoxia-ischemia.神经元五聚体蛋白1表达的基因缺失可预防新生小鼠脑缺氧缺血模型中的脑损伤。
Neurobiol Dis. 2015 Mar;75:15-30. doi: 10.1016/j.nbd.2014.12.016. Epub 2014 Dec 29.

引用本文的文献

1
Modulation of the Oxidative Stress and ICAM-1/TLR4/NF-Κβ Levels by Metformin in Intestinal Ischemia/Reperfusion Injury in Rats.二甲双胍对大鼠肠缺血/再灌注损伤中氧化应激及ICAM-1/TLR4/NF-Κβ水平的调节作用
Cell Biochem Biophys. 2025 Feb 26. doi: 10.1007/s12013-025-01687-5.
2
Role of Microglial Modulation in Therapies for Perinatal Brain Injuries Leading to Neurodevelopmental Disorders.小胶质细胞调节在治疗围产期脑损伤导致神经发育障碍中的作用。
Adv Neurobiol. 2024;37:591-606. doi: 10.1007/978-3-031-55529-9_33.
3
Metformin: The Winding Path from Understanding Its Molecular Mechanisms to Proving Therapeutic Benefits in Neurodegenerative Disorders.

本文引用的文献

1
Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy.新生儿缺氧缺血性脑病的治疗性低温疗法。
Pediatr Neonatol. 2017 Dec;58(6):475-483. doi: 10.1016/j.pedneo.2016.11.001. Epub 2017 Mar 27.
2
Daphnetin Protects against Cerebral Ischemia/Reperfusion Injury in Mice via Inhibition of TLR4/NF-B Signaling Pathway.瑞香素通过抑制TLR4/NF-κB信号通路对小鼠脑缺血/再灌注损伤起到保护作用。
Biomed Res Int. 2016;2016:2816056. doi: 10.1155/2016/2816056. Epub 2016 Dec 29.
3
Metformin Attenuates Cognitive Impairments in Hypoxia-Ischemia Neonatal Rats via Improving Remyelination.
二甲双胍：从理解其分子机制到证明其在神经退行性疾病中的治疗益处的曲折历程。
Pharmaceuticals (Basel). 2023 Dec 11;16(12):1714. doi: 10.3390/ph16121714.
4
A Mechanism of Action of Metformin in the Brain: Prevention of Methylglyoxal-Induced Glutamatergic Impairment in Acute Hippocampal Slices.二甲双胍在大脑中的作用机制：预防急性海马切片中甲基乙二醛诱导的谷氨酸能损伤。
Mol Neurobiol. 2024 Jun;61(6):3223-3239. doi: 10.1007/s12035-023-03774-1. Epub 2023 Nov 18.
5
Advances in Therapies to Treat Neonatal Hypoxic-Ischemic Encephalopathy.治疗新生儿缺氧缺血性脑病的疗法进展
J Clin Med. 2023 Oct 20;12(20):6653. doi: 10.3390/jcm12206653.
6
Further Evidence of Neuroprotective Effects of Recombinant Human Erythropoietin and Growth Hormone in Hypoxic Brain Injury in Neonatal Mice.进一步证据表明重组人促红细胞生成素和生长激素对新生鼠缺氧性脑损伤具有神经保护作用。
Int J Mol Sci. 2022 Aug 4;23(15):8693. doi: 10.3390/ijms23158693.
7
A model of metformin mitochondrial metabolism in metachromatic leukodystrophy: first description of human Schwann cells transfected with CRISPR-Cas9.异染性脑白质营养不良中二甲双胍线粒体代谢模型：首例经 CRISPR-Cas9 转染的人雪旺细胞描述。
Open Biol. 2022 Jul;12(7):210371. doi: 10.1098/rsob.210371. Epub 2022 Jul 6.
8
Ferroptosis: A Promising Therapeutic Target for Neonatal Hypoxic-Ischemic Brain Injury.铁死亡：新生儿缺氧缺血性脑损伤的有前途的治疗靶点。
Int J Mol Sci. 2022 Jul 4;23(13):7420. doi: 10.3390/ijms23137420.
9
Reduced microglia activation following metformin administration or microglia ablation is sufficient to prevent functional deficits in a mouse model of neonatal stroke.二甲双胍给药或小胶质细胞消融后小胶质细胞活化减少足以预防新生卒中小鼠模型的功能缺陷。
J Neuroinflammation. 2022 Jun 15;19(1):146. doi: 10.1186/s12974-022-02487-x.
10
Subacute metformin treatment reduces inflammation and improves functional outcome following neonatal hypoxia ischemia.亚急性二甲双胍治疗可减轻新生儿缺氧缺血后的炎症反应并改善功能预后。
Brain Behav Immun Health. 2020 Jul 25;7:100119. doi: 10.1016/j.bbih.2020.100119. eCollection 2020 Aug.
二甲双胍通过改善再髓鞘化来减轻缺氧缺血新生大鼠的认知障碍。
Cell Mol Neurobiol. 2017 Oct;37(7):1269-1278. doi: 10.1007/s10571-016-0459-8. Epub 2016 Dec 29.
4
Metformin protects the brain against ischemia/reperfusion injury through PI3K/Akt1/JNK3 signaling pathways in rats.二甲双胍通过PI3K/Akt1/JNK3信号通路保护大鼠大脑免受缺血/再灌注损伤。
Physiol Behav. 2017 Mar 1;170:115-123. doi: 10.1016/j.physbeh.2016.12.021. Epub 2016 Dec 23.
5
Peroxiredoxin 1-mediated activation of TLR4/NF-κB pathway contributes to neuroinflammatory injury in intracerebral hemorrhage.过氧化物还原酶1介导的Toll样受体4/核因子κB信号通路激活促进脑出血后的神经炎症损伤。
Int Immunopharmacol. 2016 Dec;41:82-89. doi: 10.1016/j.intimp.2016.10.025. Epub 2016 Nov 4.
6
Metformin preconditioning provide neuroprotection through enhancement of autophagy and suppression of inflammation and apoptosis after spinal cord injury.二甲双胍预处理通过增强自噬以及抑制脊髓损伤后的炎症和凋亡来提供神经保护作用。
Biochem Biophys Res Commun. 2016 Sep 2;477(4):534-540. doi: 10.1016/j.bbrc.2016.05.148. Epub 2016 May 28.
7
Pericytes of the neurovascular unit: key functions and signaling pathways.神经血管单元的周细胞：关键功能与信号通路
Nat Neurosci. 2016 May 26;19(6):771-83. doi: 10.1038/nn.4288.
8
Metformin Improves Functional Recovery After Spinal Cord Injury via Autophagy Flux Stimulation.二甲双胍通过刺激自噬通量改善脊髓损伤后的功能恢复。
Mol Neurobiol. 2017 Jul;54(5):3327-3341. doi: 10.1007/s12035-016-9895-1. Epub 2016 May 11.
9
Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury.缺氧缺血性损伤后新生儿脑的可塑性
Neural Plast. 2016;2016:4901014. doi: 10.1155/2016/4901014. Epub 2016 Mar 7.
10
Omega-3 polyunsaturated fatty acids mitigate blood-brain barrier disruption after hypoxic-ischemic brain injury.ω-3多不饱和脂肪酸可减轻缺氧缺血性脑损伤后的血脑屏障破坏。
Neurobiol Dis. 2016 Jul;91:37-46. doi: 10.1016/j.nbd.2016.02.020. Epub 2016 Feb 24.