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可溶性 Toll 样受体 2 和 4 在中风和脑出血中的潜在治疗作用。

Potential Role of Soluble Toll-like Receptors 2 and 4 as Therapeutic Agents in Stroke and Brain Hemorrhage.

机构信息

Department of Anesthesiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.

Center for Translational Research in Neurodegenerative Disease, Departments of Psychiatry, Pharmaceutics and Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.

出版信息

Int J Mol Sci. 2021 Sep 15;22(18):9977. doi: 10.3390/ijms22189977.

Abstract

Hemolysis is a physiological condition in which red blood cells (RBCs) lyse, releasing their contents into the extracellular environment. Hemolysis can be a manifestation of several diseases and conditions, such as sickle cell disease, hemorrhagic stroke, and trauma. Heme and hemoglobin are among the unique contents of RBCs that are released into the environment. Although these contents can cause oxidative stress, especially when oxidized in the extracellular environment, they can also initiate a proinflammatory response because they bind to receptors such as the Toll-like receptor (TLR) family. This review seeks to clarify the mechanism by which TLRs initiate a proinflammatory response to heme, hemoglobin, and their oxidized derivatives, as well as the possibility of using soluble TLRs (sTLRs) as therapeutic agents. Furthermore, this review explores the possibility of using sTLRs in hemorrhagic disorders in which mitigating inflammation is essential for clinical outcomes, including hemorrhagic stroke and its subtypes, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH).

摘要

溶血是一种红细胞(RBC)溶解的生理状态,导致其内容物释放到细胞外环境中。溶血可能是几种疾病和病症的表现,如镰状细胞病、出血性中风和创伤。血红素和血红蛋白是 RBC 中独特的内容物之一,它们会释放到环境中。尽管这些内容物可能会引起氧化应激,特别是在细胞外环境中氧化时,它们也可以引发炎症反应,因为它们与 TLR 家族等受体结合。本综述旨在阐明 TLR 如何引发对血红素、血红蛋白及其氧化衍生物的炎症反应的机制,以及使用可溶性 TLR(sTLR)作为治疗剂的可能性。此外,本综述还探讨了在需要减轻炎症以改善临床结果的出血性疾病中使用 sTLR 的可能性,这些疾病包括出血性中风及其亚型、脑出血(ICH)和蛛网膜下腔出血(SAH)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55c4/8470802/532cd01b8dd4/ijms-22-09977-g001.jpg

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