本文關鍵詞： 高遷移率族蛋白1A盒/B盒 LBPK95A 原核表達 人單核細胞 腫瘤壞死因子α 膿毒癥　出處：《第四軍醫(yī)大學》2005年碩士論文　論文類型：學位論文

【摘要】：脂多糖(LPS)是革蘭陰性菌(GNB)細胞壁的主要成份,是GNB所致膿毒癥多種病理生理反應的第一觸發(fā)因子。其引起的膿毒癥和膿毒性休克是嚴重危及生命的全身性炎性反應綜合征,致死率在兒童及成年人中分別達10～15%和40%左右。探討膿毒癥的新的有效防治途徑無疑具有重要意義。近年研究發(fā)現(xiàn),高遷移率族蛋白1(HMGB1)作為膿毒癥潛在的晚期炎癥介質參與了內毒素的致病過程,是膿毒癥致死效應的重要炎癥介質,對HMGB1干預可有效阻止膿毒癥。HMGB1結構域B盒在炎癥過程中的生物學功能與全長HMGB1相似,在HMGB1的致炎作用中發(fā)揮巨大作用。HMGB1結構域A盒具有類似HMGB1抗體的作用,可抑制細胞外HMGB1的活性,減少TNF-α等炎癥介質的釋放,控制膿毒癥的發(fā)生發(fā)展。LPS結合蛋白(LBP)作為LPS的轉運蛋白,控制著LPS誘導的單核/巨噬細胞炎性反應。LBP結構域LBPK95A可阻斷LPS與LBP的結合,抑制LPS的細胞毒作用。如果將HMGB1 A盒和LBPK95A兩者結合起來,從膿毒癥的級聯(lián)反應的早期和晚期進行干預,有可能為膿毒癥的防治提供新的有效途徑。為此本課題進行了以下主要研究:鼠高遷移率族蛋白1結構域A盒、B盒編碼序列的克隆和原核表達及生物學活性鑒定;HMGB1A盒與LBPK95A融合基因的表達及純化;A-LBP融合蛋白生物學功能的初步研究。 一、HMGB1 A盒及B盒編碼序列的克隆表達、產物純化和活性鑒定
[Abstract]:Lipopolysaccharide (LPS) is the main component of the cell wall of Gram-negative bacteria (GNB). Sepsis and septic shock are the first trigger factors of pathophysiological responses to sepsis induced by GNB, which is a serious life-threatening systemic inflammatory response syndrome. The mortality rate in children and adults is about 1015% and 40% respectively. It is of great significance to explore the new effective prevention and treatment of sepsis. High mobility group protein (HMGB1), as a potential late inflammatory mediator of sepsis, plays an important role in the pathogenesis of endotoxin and plays an important role in the lethal effect of sepsis. Intervention with HMGB1 could effectively prevent the biological function of sepsis. HMGB1 domain B box in inflammatory process similar to that of full-length HMGB1. HMGB1 domain A box has the similar effect of HMGB1 antibody and can inhibit the activity of extracellular HMGB1. Reduce the release of inflammatory mediators such as TNF- 偽, and control the occurrence and development of sepsis. LPS-binding protein (LBP) is the transporter of LPS. Control of monocyte / macrophage inflammatory response induced by LPS. LBP domain LBPK95A could block the binding of LPS to LBP. Inhibits the cytotoxicity of LPS. If you combine HMGB1 A box with LBPK95A, you can intervene in the early and late stages of the cascade of sepsis. It is possible to provide a new effective way for the prevention and treatment of sepsis. Therefore, this paper has carried out the following main research: mouse high mobility group protein 1 domain A box. Cloning, prokaryotic expression and biological activity identification of B box coding sequence; Expression and purification of HMGB1A cassette and LBPK95A fusion gene; Preliminary study on biological function of A-LBP fusion protein. Cloning, expression, purification and activity Identification of coding sequences of HMGB1 A Box and B Box
【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2005
【分類號】：R346

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