| 王明宇,王雯雯,查旭东,刘聪.靶向Toll样受体通路辐射防护剂研究进展[J].中华放射医学与防护杂志,2019,39(7):549-553 |
| 靶向Toll样受体通路辐射防护剂研究进展 |
| Progresses in radiation protective agents targeting Toll-like receptor pathway |
| 投稿时间：2019-03-27 |
| DOI：10.3760/cma.j.issn.0254-5098.2019.07.013 |
| 中文关键词: 辐射防护 NF-κB Toll样受体 |
| 英文关键词:Radioprotection NF-κB Toll-like receptors |
| 基金项目:国家自然科学基金（81872559，81573092） |
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| 摘要点击次数: 2463 |
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| 中文摘要: |
| 急性辐射暴露通常会导致急性放射综合征，包括造血、消化、皮肤、心血管和神经系统等组织广泛的细胞凋亡、坏死和自噬。在肿瘤细胞中，凋亡机制受到抑制或者丧失，其增殖能力便会显著增强，与其能力相关的途径包含有p53和NF-κB途径。Toll样受体（toll-like receptors，TLR）是一类参与机体非特异性免疫的蛋白质分子，激活后能够上调NF-κB途径，使得细胞放射抵抗能力显著增加。TLR4具有基础的细胞辐射损伤防护效应。传统的TLR4激动剂拥有较多的不良反应限制了其临床应用，近来相继发现了一些具有低不良反应率和高效辐射防护作用的TLRs激动剂。相比于其他亚型，TLR2、TLR4、TLR5和TLR9在细胞辐射损伤防护中的效果表现得更为明显，其相关配体包括细菌脂蛋白（BLP）、热灭活的鼠伤寒沙门氏菌（HKST）、细菌鞭毛蛋白和TLR9受体激动剂等。不过，不同的TLR识别病原体的特定组分并启动不同的下游信号传导途径，其防护效应也随之不同。 |
| 英文摘要: |
| Acute radiation exposure usually causes severe dysfunction in various tissues of the organism, among which hematopoiesis, digestion, skin, cardiovascular and nervous system are most obviously affected, often leading to extensive apoptosis and acute radiation syndrome. Apoptosis inhibition or loss could increase proliferation of tumor cells through p53 and NF-κB pathways. Toll-like receptors (TLRs) are a class of protein molecules involved in non-specific immunity. Up-regulation of the NF-κB pathway results in a significant increase in the radioresistance of cells. TLR4 has a basal cell radiation damage protection effect. Traditional TLR4 agonist lipopolysaccharide is limited in clinical application due to severe toxicity. Recently, some new TLRs agonists have been reported, which have protective effects against the lethal effects of ionizing radiation and lower toxic side effects. Among them, TLR2, TLR4, TLR5 and TLR9 play key roles in radiation protection, such as TLR2 receptor agonist bacterial lipoprotein (BLP), TLR4 receptor agonist heat-activated Salmonella typhimurium (HKST), TLR5 receptor agonism Bacterial flagellin and TLR9 receptor agonist. However, those different TLRs recognize specific components of the pathogen and thus initiate different downstream signaling pathways with different protective effects. |
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