内毒素耐受的机制研究

The Study on Endotoxin Tolerance Mechanisms

内毒素是革兰阴性菌细胞壁的成分,能够激发机体的免疫反应。当细菌释放大量的内毒素到血液,即可引起内毒素血症,内毒素血症可以伴随多种疾病出现,引起致死性感染性休克,循环功能衰竭,其病死率极高。内毒素耐受是指机体接受小剂量内毒素刺激后对后续内毒素刺激的反应性降低,表现为促炎因子释放减少而抗炎因子释放增加,机体发热,缺氧,低血压,休克的症状减轻。内毒素耐受的发生机制极其复杂,受机体内多种因素的调节,但目前尚无明确的结论。近年来,有关其机制的研究有许多报道,其中,对内毒素耐受的信号机制的研究最为广泛,大量的研究表明内毒素的主要受体,细胞内的信号蛋白,负调控因子以及转录因子可能在内毒素耐受的发生过程中起重要作用。也有报道表明免疫细胞的凋亡,染色体修饰和基因重排以及小RNA的参与可能诱导内毒素耐受的发生。本文从细胞、分子水平对内毒素耐受的发生机制进行综述,拟对炎症性疾病如内毒素血症的预防和治疗提供理论依据。

Endotoxin, the component of cell wall for Gram-negative bacteria, has been reported to be a potential risk factor of immune response. Endotoxemia occured when bacterial endotoxin released into the blood and accompanied by a variety of diseases.Endotoxemia can cause fatal septic shock and circulatory failure which result in high mortality rate. Endotoxin tolerance is described as the body become refractory to subsequent endotoxin challenge if it has been previously exposured to a sublethal injection of endotoxin,which is characterized by decreased production of proinflammatory cytokins and increased secretion of anti-inflammatory mediators. The symptoms like heat, hypoxia, hypotension and shock are ameliorated in endotoxin tolerance. The mechanisms underlying endotoxin tolerance are extremely complex which remain elusive even though various studies have worked on it in recent years. Signaling regulatory mechanisms which implicated that the receptors, signaling moleculars, negative regulators and transcription factors have involved in endotoxin tolerance are reported widely. Moreover, immune cell apoptosis, chromatin modification and gene reprogramming as well as the involvement of micro RNA may also contribute to regulate endotoxin tolerance. This review considerably advances our understanding of the mechanism of endotoxin tolerance from cellular and molecular level in order to provide new theoretical basis for prevention and treatment of inflammatory diseases such as endotoxemia.