• 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

小胶质细胞衍生的 NLRP3 激活介导应激诱导高血压大鼠延髓腹外侧区前胰蛋白酶激活的升压作用。

Microglia-Derived NLRP3 Activation Mediates the Pressor Effect of Prorenin in the Rostral Ventrolateral Medulla of Stress-Induced Hypertensive Rats.

机构信息

Laboratory of Neuropharmacology and Neurotoxicology, Shanghai Key Laboratory of Bio-Energy Crops, College of Life Science, Shanghai University, Shanghai, 200444, China.

Department of Physiology and Pathophysiology, Basic Medicine College, Fudan University, Shanghai, 200032, China.

出版信息

Neurosci Bull. 2020 May;36(5):475-492. doi: 10.1007/s12264-020-00484-9. Epub 2020 Apr 3.

DOI:10.1007/s12264-020-00484-9
PMID:32242284
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7186257/
Abstract

Increased microglial activation and neuroinflammation within autonomic brain regions such as the rostral ventrolateral medulla (RVLM) have been implicated in stress-induced hypertension (SIH). Prorenin, a member of the brain renin-angiotensin system (RAS), can directly activate microglia. The present study aimed to investigate the effects of prorenin on microglial activation in the RVLM of SIH rats. Rats were subjected to intermittent electric foot-shocks plus noise, this stress was administered for 2 h twice daily for 15 consecutive days, and mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) were monitored. The results showed that MAP and RSNA were augmented, and this paralleled increased pro-inflammatory phenotype (M1) switching. Prorenin and its receptor (PRR) expression and the NLR family pyrin domain containing 3 (NLRP3) activation were increased in RVLM of SIH rats. In addition, PLX5622 (a microglial depletion agent), MCC950 (a NLRP3 inhibitor), and/or PRO20 (a (Pro)renin receptor antagonist) had antihypertensive effects in the rats. The NLRP3 expression in the RVLM was decreased in SIH rats treated with PLX5622. Mito-tracker staining showed translocation of NLRP3 from mitochondria to the cytoplasm in prorenin-stimulated microglia. Prorenin increased the ROS-triggering M1 phenotype-switching and NLRP3 activation, while MCC950 decreased the M1 polarization. In conclusion, upregulated prorenin in the RVLM may be involved in the pathogenesis of SIH, mediated by activation of the microglia-derived NLRP3 inflammasome. The link between prorenin and NLRP3 in microglia provides insights for the treatment of stress-related hypertension.

摘要

在自主脑区（如延髓头端腹外侧区 [RVLM]）中，小胶质细胞的激活和神经炎症增加与应激诱导的高血压（SIH）有关。脑肾素-血管紧张素系统（RAS）的成员前肾素可以直接激活小胶质细胞。本研究旨在探讨前肾素对 SIH 大鼠 RVLM 中小胶质细胞激活的影响。大鼠接受间歇性电击加噪声，这种应激每天两次，每次 2 小时，连续 15 天，监测平均动脉压（MAP）和肾交感神经活性（RSNA）。结果表明，MAP 和 RSNA 增加，这与促炎表型（M1）转换增加平行。前肾素及其受体（PRR）表达和 NOD、LRP 和pyrin 结构域包含蛋白 3（NLRP3）激活在 SIH 大鼠的 RVLM 中增加。此外，PLX5622（一种小胶质细胞耗竭剂）、MCC950（一种 NLRP3 抑制剂）和/或 PRO20（一种（Pro）肾素受体拮抗剂）在大鼠中具有降压作用。在接受 PLX5622 治疗的 SIH 大鼠中，RVLM 中的 NLRP3 表达减少。Mito-tracker 染色显示，前肾素刺激的小胶质细胞中 NLRP3 从线粒体易位到细胞质。前肾素增加了 ROS 触发的 M1 表型转换和 NLRP3 激活，而 MCC950 则减少了 M1 极化。总之，RVLM 中上调的前肾素可能参与了 SIH 的发病机制，其介导方式是小胶质细胞源性 NLRP3 炎性小体的激活。小胶质细胞中前肾素与 NLRP3 之间的联系为应激相关高血压的治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/c07f2c9bfb83/12264_2020_484_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/f631d59fea87/12264_2020_484_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/d5c0c4de84bd/12264_2020_484_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/ffca04f3daea/12264_2020_484_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/b95d71847749/12264_2020_484_Fig4a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/a711fdaa5110/12264_2020_484_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/e9b208946362/12264_2020_484_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/8b36d4b0c4c8/12264_2020_484_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/aa4cc412d967/12264_2020_484_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/c07f2c9bfb83/12264_2020_484_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/f631d59fea87/12264_2020_484_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/d5c0c4de84bd/12264_2020_484_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/ffca04f3daea/12264_2020_484_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/b95d71847749/12264_2020_484_Fig4a_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/a711fdaa5110/12264_2020_484_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/e9b208946362/12264_2020_484_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/8b36d4b0c4c8/12264_2020_484_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/aa4cc412d967/12264_2020_484_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9df4/7186295/c07f2c9bfb83/12264_2020_484_Fig9_HTML.jpg

相似文献

1
Microglia-Derived NLRP3 Activation Mediates the Pressor Effect of Prorenin in the Rostral Ventrolateral Medulla of Stress-Induced Hypertensive Rats.小胶质细胞衍生的 NLRP3 激活介导应激诱导高血压大鼠延髓腹外侧区前胰蛋白酶激活的升压作用。
Neurosci Bull. 2020 May;36(5):475-492. doi: 10.1007/s12264-020-00484-9. Epub 2020 Apr 3.
2
Sigma-1 Receptor Activation Suppresses Microglia M1 Polarization via Regulating Endoplasmic Reticulum-Mitochondria Contact and Mitochondrial Functions in Stress-Induced Hypertension Rats.西格玛-1受体激活通过调节应激诱导高血压大鼠的内质网-线粒体接触及线粒体功能来抑制小胶质细胞M1极化。
Mol Neurobiol. 2021 Dec;58(12):6625-6646. doi: 10.1007/s12035-021-02488-6. Epub 2021 Oct 2.
3
HMGB1/RAGE axis mediates stress-induced RVLM neuroinflammation in mice via impairing mitophagy flux in microglia.高迁移率族蛋白 B1/晚期糖基化终产物受体轴通过损害小胶质细胞中的线粒体自噬流介导应激诱导的 RVLM 神经炎症。
J Neuroinflammation. 2020 Jan 10;17(1):15. doi: 10.1186/s12974-019-1673-3.
4
Neuroinflammation contributes to autophagy flux blockage in the neurons of rostral ventrolateral medulla in stress-induced hypertension rats.神经炎症导致应激诱导高血压大鼠延髓头端腹外侧区神经元自噬流阻断。
J Neuroinflammation. 2017 Aug 23;14(1):169. doi: 10.1186/s12974-017-0942-2.
5
Selective NLRP3 inflammasome inhibitor reduces neuroinflammation and improves long-term neurological outcomes in a murine model of traumatic brain injury.选择性 NLRP3 炎性体抑制剂可减少创伤性脑损伤小鼠模型的神经炎症并改善长期神经预后。
Neurobiol Dis. 2018 Sep;117:15-27. doi: 10.1016/j.nbd.2018.05.016. Epub 2018 May 30.
6
Microglia-derived TNF-α contributes to RVLM neuronal mitochondrial dysfunction via blocking the AMPK-Sirt3 pathway in stress-induced hypertension.小胶质细胞衍生的 TNF-α 通过阻断应激诱导的高血压中 AMPK-Sirt3 通路导致 RVLM 神经元线粒体功能障碍。
J Neuroinflammation. 2023 Jun 1;20(1):137. doi: 10.1186/s12974-023-02818-6.
7
Activation of P2XR- NLRP3 pathway in Retinal microglia contribute to Retinal Ganglion Cells death in chronic ocular hypertension (COH).P2XR-NLRP3 通路在视网膜小胶质细胞中的激活导致慢性眼压升高（COH）中的视网膜神经节细胞死亡。
Exp Eye Res. 2019 Nov;188:107771. doi: 10.1016/j.exer.2019.107771. Epub 2019 Aug 22.
8
Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension.NLRP3 炎性小体的药理学抑制可降低盐敏感性高血压患者的血压、肾脏损伤和功能障碍。
Cardiovasc Res. 2019 Mar 15;115(4):776-787. doi: 10.1093/cvr/cvy252.
9
Repeated electroacupuncture attenuating of apelin expression and function in the rostral ventrolateral medulla in stress-induced hypertensive rats.电针反复刺激减轻应激诱导高血压大鼠延髓头端腹外侧区 Apelin 的表达和功能。
Brain Res Bull. 2013 Aug;97:53-62. doi: 10.1016/j.brainresbull.2013.05.013. Epub 2013 Jun 7.
10
IFN-γ deficiency in the rostral ventrolateral medulla contributes to stress-induced hypertension by impairing microglial synaptic engulfment.延髓头端腹外侧部的γ-干扰素缺乏通过损害小胶质细胞的突触吞噬作用导致应激性高血压。
J Hypertens. 2023 Aug 1;41(8):1323-1332. doi: 10.1097/HJH.0000000000003470. Epub 2023 May 23.

引用本文的文献

1
Angiotensin-(1-7) Mitigates Progression from Acute Kidney Injury to Chronic Kidney Disease Via Renin-Angiotensin System Modulation in a Murine Model.血管紧张素-（1-7）通过调节小鼠模型中的肾素-血管紧张素系统减轻急性肾损伤向慢性肾病的进展。
Inflammation. 2025 Aug 26. doi: 10.1007/s10753-025-02341-1.
2
FOXO3-induced microRNA-128-3p promotes the progression of spinal cord injury in mice via regulating NLRP3 inflammasome-mediated pyroptosis.FOXO3诱导的微小RNA-128-3p通过调节NLRP3炎性小体介导的细胞焦亡促进小鼠脊髓损伤的进展。
Front Immunol. 2025 Feb 21;16:1526721. doi: 10.3389/fimmu.2025.1526721. eCollection 2025.
3

本文引用的文献

1
Melatonin decreases M1 polarization via attenuating mitochondrial oxidative damage depending on UCP2 pathway in prorenin-treated microglia.褪黑素通过依赖于 UCP2 途径的线粒体氧化损伤衰减减少原啡肽处理的小胶质细胞中的 M1 极化。
PLoS One. 2019 Feb 11;14(2):e0212138. doi: 10.1371/journal.pone.0212138. eCollection 2019.
2
Microglia: Neuroimmune-sensors of stress.小胶质细胞：应激的神经免疫传感器。
Semin Cell Dev Biol. 2019 Oct;94:176-185. doi: 10.1016/j.semcdb.2019.01.001. Epub 2019 Jan 9.
3
Calcitriol inhibits ROS-NLRP3-IL-1β signaling axis via activation of Nrf2-antioxidant signaling in hyperosmotic stress stimulated human corneal epithelial cells.
The role of (pro)renin receptor and its soluble form in cardiovascular diseases.
（前）肾素受体及其可溶性形式在心血管疾病中的作用。
Front Cardiovasc Med. 2023 Feb 2;10:1086603. doi: 10.3389/fcvm.2023.1086603. eCollection 2023.
4
Regulation of Glial Function by Noncoding RNA in Central Nervous System Disease.非编码 RNA 对中枢神经系统疾病中神经胶质功能的调控
Neurosci Bull. 2023 Mar;39(3):440-452. doi: 10.1007/s12264-022-00950-6. Epub 2022 Sep 26.
5
Inhibition of cGAS in Paraventricular Nucleus Attenuates Hypertensive Heart Injury Via Regulating Microglial Autophagy.室旁核中 cGAS 的抑制通过调节小胶质细胞自噬减轻高血压心脏损伤。
Mol Neurobiol. 2022 Nov;59(11):7006-7024. doi: 10.1007/s12035-022-02994-1. Epub 2022 Sep 7.
6
Noise exposure and its relationship with postinfarction cardiac remodeling: implications for NLRP3 inflammasome activation.噪声暴露及其与梗死后心脏重构的关系：对 NLRP3 炎性小体激活的影响。
Bioengineered. 2022 May;13(5):12127-12140. doi: 10.1080/21655979.2022.2073126.
7
SIRT1 Promotes M2 Microglia Polarization Reducing ROS-Mediated NLRP3 Inflammasome Signaling After Subarachnoid Hemorrhage.SIRT1 促进 M2 小胶质细胞极化，减少蛛网膜下腔出血后 ROS 介导的 NLRP3 炎症小体信号。
Front Immunol. 2021 Nov 24;12:770744. doi: 10.3389/fimmu.2021.770744. eCollection 2021.
8
PLIN2 Mediates Neuroinflammation and Oxidative/Nitrosative Stress via Downregulating Phosphatidylethanolamine in the Rostral Ventrolateral Medulla of Stressed Hypertensive Rats.PLIN2通过下调应激性高血压大鼠延髓头端腹外侧区的磷脂酰乙醇胺介导神经炎症和氧化/亚硝化应激。
J Inflamm Res. 2021 Nov 30;14:6331-6348. doi: 10.2147/JIR.S329230. eCollection 2021.
9
Microglial activation induced by LPS mediates excitation of neurons in the hypothalamic paraventricular nucleus projecting to the rostral ventrolateral medulla.LPS 诱导的小胶质细胞活化介导投射到延髓头端腹外侧区的下丘脑室旁核神经元的兴奋。
BMB Rep. 2021 Dec;54(12):620-625. doi: 10.5483/BMBRep.2021.54.12.105.
10
Sigma-1 Receptor Activation Suppresses Microglia M1 Polarization via Regulating Endoplasmic Reticulum-Mitochondria Contact and Mitochondrial Functions in Stress-Induced Hypertension Rats.西格玛-1受体激活通过调节应激诱导高血压大鼠的内质网-线粒体接触及线粒体功能来抑制小胶质细胞M1极化。
Mol Neurobiol. 2021 Dec;58(12):6625-6646. doi: 10.1007/s12035-021-02488-6. Epub 2021 Oct 2.
骨化三醇通过激活 Nrf2-抗氧化信号抑制高渗应激刺激的人角膜上皮细胞中的 ROS-NLRP3-IL-1β 信号轴。
Redox Biol. 2019 Feb;21:101093. doi: 10.1016/j.redox.2018.101093. Epub 2018 Dec 26.
4
Human immunodeficiency virus Type-1 single-stranded RNA activates the NLRP3 inflammasome and impairs autophagic clearance of damaged mitochondria in human microglia.人类免疫缺陷病毒 1 型单链 RNA 激活 NLRP3 炎性体，并损害人小胶质细胞中受损线粒体的自噬清除。
Glia. 2019 May;67(5):802-824. doi: 10.1002/glia.23568. Epub 2018 Dec 24.
5
CD4 Regulatory T Lymphocytes Prevent Impaired Cerebral Blood Flow in Angiotensin II-Induced Hypertension.CD4 调节性 T 淋巴细胞可预防血管紧张素Ⅱ诱导的高血压中脑血流受损。
J Am Heart Assoc. 2019 Jan 8;8(1):e009372. doi: 10.1161/JAHA.118.009372.
6
Inflammasome-Independent Role of NLRP3 Mediates Mitochondrial Regulation in Renal Injury.NLRP3 通过炎症小体非依赖机制调控肾脏损伤中线粒体功能。
Front Immunol. 2018 Nov 12;9:2563. doi: 10.3389/fimmu.2018.02563. eCollection 2018.
7
Effect of NAC treatment and physical activity on neuroinflammation in subchronic Parkinsonism; is physical activity essential?NAC 治疗和身体活动对亚慢性帕金森病神经炎症的影响；身体活动是否必不可少？
J Neuroinflammation. 2018 Nov 26;15(1):328. doi: 10.1186/s12974-018-1357-4.
8
Pharmacological inhibition of the NLRP3 inflammasome reduces blood pressure, renal damage, and dysfunction in salt-sensitive hypertension.NLRP3 炎性小体的药理学抑制可降低盐敏感性高血压患者的血压、肾脏损伤和功能障碍。
Cardiovasc Res. 2019 Mar 15;115(4):776-787. doi: 10.1093/cvr/cvy252.
9
Heme oxygenase-1 protects airway epithelium against apoptosis by targeting the proinflammatory NLRP3-RXR axis in asthma.血红素加氧酶-1 通过靶向哮喘中的促炎 NLRP3-RXR 轴保护气道上皮细胞免于细胞凋亡。
J Biol Chem. 2018 Nov 30;293(48):18454-18465. doi: 10.1074/jbc.RA118.004950. Epub 2018 Oct 17.
10
Angiotensin-Converting Enzyme 2 in the Rostral Ventrolateral Medulla Regulates Cholinergic Signaling and Cardiovascular and Sympathetic Responses in Hypertensive Rats.延髓头端腹外侧区血管紧张素转换酶 2 调节高血压大鼠的胆碱能信号和心血管及交感神经反应。
Neurosci Bull. 2019 Feb;35(1):67-78. doi: 10.1007/s12264-018-0298-3. Epub 2018 Oct 15.