本文選題：高遷移率組蛋白B1　切入點：Fas　出處：《濟南大學》2013年碩士論文　論文類型：學位論文

【摘要】：目的繼發(fā)性腦損傷是急性顱腦損傷預后不良的重要因素，腦損傷所引起的腦部和全身的炎癥反應的研究和治療成了臨床腦外傷治療的又一個重要關(guān)鍵點。高遷移率組蛋白B1(High-mobility group box1，HMGB1)在炎癥反應中起重要作用，是感染的晚期階段被釋放的炎癥因子，但目前研究發(fā)現(xiàn)其在腦外傷早期就被大量釋放，這一機制目前尚未明確。研究證實， FasL在腦損傷過程中扮演極其重要作用，抑制FasL的作用可以明顯減輕腦損傷。Fas(CD95)是傳統(tǒng)凋亡受體，以往學者都試圖用Fas所導致的致凋亡作用來解釋FasL在腦損傷中的作用，有學者在多倫多大學炎癥與創(chuàng)傷研究中心發(fā)現(xiàn)，F(xiàn)asL（CD178）可以刺激巨噬細胞主動釋放HMGB1，這種釋放是一個迅速發(fā)生的過程。我們提出這樣一種假設：在顱腦損傷早期，F(xiàn)as可通過HMGB1大量釋放（非凋亡機制）引起炎癥發(fā)應導致繼發(fā)性顱腦損傷。本研究旨在探討急性顱腦損傷患者血清中HMGB1與Fas的表達及內(nèi)部聯(lián)系，進一步明確繼發(fā)性顱腦損傷發(fā)生發(fā)展的機制，為顱腦損傷的治療提供新思路。 方法選擇2011年7月至2013年01月在我院就診的急性顱腦損傷患者62例，，根據(jù)患者入院時格拉斯哥昏迷評分(Glasgow coma score GCS)將其分為輕度組（GCS評分＞12分）、中度組（8分＜GCS評分≤12分）和重度組（GCS評分≤8分），選擇正常健康志愿者15例做為對照組。所有患者入院后即采集外周靜脈血，分離血清，采用雙抗體夾心酶聯(lián)免疫分析法(Enzyme Linked-Immuno-SorbentAssay，ELISA)測定血中HMGB1及Fas含量。采用統(tǒng)計學軟件SPSS17.0對所得數(shù)據(jù)進行處理，并對兩組數(shù)據(jù)進行相關(guān)性分析，P0.05為差異有統(tǒng)計學意義。 結(jié)果 1、急性顱腦損傷患者血清中HMGB1水平：輕度組為5.23±0.065ng/ml，中度組為8.47±0.075ng/ml，重度組為10.56±0.82ng/ml，對照組為3.54±0.13ng/ml。各組之間差異有統(tǒng)計學意義（P＜0.05）。 2、急性顱腦損傷患者血清中Fas水平：輕度組為2.83±0.13pg/ml，中度組為4.55±0.13μpg/ml重度組為7.31±0.19pg/ml，對照組為1.10±0.63pg/ml，各組之間差異有統(tǒng)計學意義（P＜0.05）。 3、相關(guān)分析發(fā)現(xiàn)急性顱腦損傷患者血清中Fas和HMGB1水平呈正線性相關(guān)關(guān)系，r=0.875，P＜0.05。 結(jié)論 1、急性顱腦損傷患者血清中HMGB1和Fas可判斷患者病情輕重。 2、急性顱腦損傷患者血清中Fas的升高可能是通過HMGB1-炎癥反應途徑導致繼發(fā)性顱腦損傷。
[Abstract]:Objective Secondary brain injury is an important factor in poor prognosis of acute brain injury. The study and treatment of brain and systemic inflammation induced by brain injury has become another key point in the treatment of brain trauma. High mobility group box 1 HMGB1 plays an important role in the inflammatory response. It is an inflammatory factor released in the late stage of infection, but it has been found to be released in large quantities in the early stage of brain injury. This mechanism is not clear at present. It has been confirmed that FasL plays an extremely important role in the process of brain injury. Inhibition of FasL can significantly reduce brain injury. Fas-CD95) is a traditional apoptotic receptor. Previous scholars have tried to explain the role of FasL in brain injury by using the apoptosis-induced effect of Fas. Some researchers at the Center for inflammation and Trauma of the University of Toronto have found that FasL CD178) stimulates the active release of HMGB1 from macrophages, which is a rapid process. We propose a hypothesis that FAS can be activated in the early stages of craniocerebral injury. Excessive release of HMGB1 (non-apoptotic mechanism) may induce inflammation and lead to secondary craniocerebral injury. The purpose of this study was to investigate the expression of HMGB1 and Fas in serum of patients with acute craniocerebral injury. To further clarify the mechanism of the occurrence and development of secondary craniocerebral injury and provide a new way for the treatment of craniocerebral injury. Methods 62 patients with acute craniocerebral injury were selected from July 2011 to January 2013. According to the Glasgow coma score score on admission, the patients were divided into mild group (GCS > 12), moderate group (8 < GCS 鈮

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