本文關(guān)鍵詞：高遷移率族蛋白B1在COPD病人支氣管肺泡灌洗液中的表達及其意義，由筆耕文化傳播整理發(fā)布。

        研究背景：慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）是一種全球性患病率和死亡率很高而病因及發(fā)病機制尚不完全清楚的疾病。COPD主要累及肺臟，但也可引起全身的不良效應(yīng)。COPD特征性的病理改變存在于中央氣道、外周氣道、肺實質(zhì)和肺血管系統(tǒng)。病理改變包括慢性炎癥，，表現(xiàn)為肺組織不同部位特定的炎癥細胞增加，以及由于反復(fù)損傷和修復(fù)引起的結(jié)構(gòu)變化，即氣道重塑。COPD的發(fā)病機制尚未完全明了。目前普遍認為是蛋白酶-抗蛋白酶失衡、氧化-抗氧化失衡及氣道慢性炎癥等因素共同作用的結(jié)果。炎癥在COPD的發(fā)病機制中處于中心地位�，F(xiàn)已明確多種炎癥細胞和氣道結(jié)構(gòu)細胞以及其分泌的多種炎癥介質(zhì)參與慢性氣道炎癥、氣道重塑的發(fā)生發(fā)展。高遷移率族蛋白B1（highmobility group box-1protein,HMGB1）是一種普遍存在的高度保守的核蛋白，參與DNA的轉(zhuǎn)錄、復(fù)制、修復(fù)以及炎癥反應(yīng)等。目前相關(guān)研究表明，HMGB1在COPD的發(fā)病機制中扮演著重要角色。在COPD病人氣道中，氣道炎癥細胞如巨噬細胞，單核細胞和氣道結(jié)構(gòu)細胞如上皮細胞，平滑肌細胞高水平表達并分泌HMGB1，而HMGB1又可促進其他致炎癥細胞因子的釋放，促進氣道炎癥的發(fā)生。本研究提取COPD患者的支氣管肺泡灌洗液并分析灌洗液中HMGB1的含量及其他炎癥因子的含量，初步探討HMGB1在COPD中的作用。目的：通過測定COPD患者的支氣管肺泡灌洗液中HMGB1的含量，初步探討HMGB1在COPD氣道炎癥中的作用。方法：將研究對象分為疾病組和對照組，分別行支氣管鏡檢查并支氣管肺泡灌洗術(shù)，提取支氣管肺泡灌洗液。分析兩組灌洗液的細胞計數(shù)及分類，用酶聯(lián)免疫吸附法測定（ELISA）測定HMGB1，IL-1β，IL-8及TNF-α的含量，分析HMGB1和其他炎癥因子間的關(guān)系，并分析HMGB1和疾病嚴重程度間的關(guān)系。結(jié)果：對照組和COPD組BALF（支氣管肺泡灌洗液）中的細胞總數(shù)、單核巨噬細胞及中性粒細胞百分比分別為0.74（0.23-1.46）×10~9/L，89.2（34.1-96.6）%，8.0（1.3-17.2）%；4.16（0.94-9.73）×109/L，58.3（25.2-74.0）%，33.4(19.6-57.9)%。和對照組相比，COPD組BALF的細胞總數(shù)、中性粒細胞百分比較高，二者有顯著性差異(P <0.05)，而單核巨噬細胞較低，二者有顯著性差異(P <0.05)。對照組和COPD組BALF中的淋巴細胞百分分別為2.4（3.6-8.6）%、2.7(4.3-9.7)%，兩組差異無統(tǒng)計學(xué)意義（p＞0.05）。COPD組和對照組BALF中HMGB1(ug/L)、IL-1β（ng/L），TNF-α（ng/L）及IL-8（ng/L）的含量分別為8.95(0.01-32.00)，3.62(0.01-11.30)，0.97（0.35-14.50），3.45(0.01-19.96)/2.35(0.01-29.00)，0.45(0.01-5.56)，0.56（0.01-3.50），3.16(0.01-19.54)。 COPD組HMGB1, IL-1β, TNF-α顯著高于對照組（P<0.05），且HMGB1的含量和IL-1β、TNF-α呈線性相關(guān)（r=0.685及0.624，P均<0.05）。在COPD組中，中重度病人BALF中HMGB1含量顯著高于輕度病人（P<0.05）。結(jié)論：COPD病人支氣管肺泡灌洗液中HMGB1的表達明顯增高，與疾病的嚴重程度具有一定的關(guān)聯(lián)性。支氣管肺泡灌洗液中HMGB1的含量和IL-1β、TNF-α等炎癥因子的含量具有顯著相關(guān)性。

    Research background：chronic obstructive pulmonary disease(COPD) is a diseasethat the etiological factor and pathogenesis are not understood entirely，with highprevalence rate and mortality rate.It mainly involve the lung as well as whole system.The characteristic pathology locating in center and peripheral airways, lung parenchyma, pulmonary vasculature contain chronic inflammation that displayincremental inflammatory cell in lung and airway remodeling induced repeating lesionand restore. The pathogenesis of COPD is not very clear.The current view to thepathogenesis of COPD that the disbalance of protease-antiprotease and the disbalanceof oxidation-antioxydation as well as the chronic airway inflammation commonlyinduce the pathological change.inflammation that involve multiple inflammatory cells,airway structural cells and inflammatory mediators is in center of pathogenesis. Highmobility group box-1protein is a highly conserved prevalent nuclear protein whichparticipates in DNA transcription, replication, repairment and inflammatoryreactions.It is studied that HMGB1acts as a leading role in the pathogenesis ofCOPD.One hand,the airway inflammatory cells such as macrophagocyte, monocytesand airway structural cells such as epithelial cells, smooth muscle cells express andsecret grossly HMGB1,on the other hand,HMGB1can promote release ofinflammatory cytokines that advance airway inflammation. In the research we abstractthe bronchoalveolar lavage fluid(BALF) of patient suffering COPD and measure andanalysis the content of HMGB1and other inflammatory cytokine in BALF so as toexplore the effection of HMGB1to the COPD.Objective: By evaluate HMGB1in the BALF of patient suffering COPD, we exploreinitially the effect of HMGB1to the characteristic pathology of COPD: airwayinflammation.Methods:The objects that were grouped patient group and control group were alveolarwashed respectively and the bronchoalveolar lavage fluid was extracted. Analysing thecell counting and classification of two group BLAF and assaying the HMGB1, IL-1β，IL-8and TNF-αin BLAF with ELISA assay. The correlation between HMGB1andother inflammatory factor as well as severity of desease was evaluated and analysed. Results:The total cell counting, mononuclear macrophage counting, neutrophilicgranulocyte counting in BLAF of control group were respectively0.74（0.23-1.46）×10~9/L，89.2（34.1-96.6）%，8.0（1.3-17.2）%.It were4.16（0.94-9.73）×109/L，58.3（25.2-74.0）%，33.4(19.6-57.9)%in BALF of patient group. The total cellcounting, neutrophilic granulocyte counting in BLAF of patient group weresignificantly higher than control group (P<0.05). Reversely,the former is lowerthan thelatter in mononuclear macrophage counting(P<0.05). The lymphocyte counting inBALF of patient group and control group was respectively2.4（3.6-8.6）%、2.7(4.3-9.7)%,the two group have no significant difference(P>0.05).The concentrationof HMGB1(ug/L), IL-1β（ng/L），TNF-α（ng/L）,IL-8（ng/L） in BALF of patient groupand control group were respectively8.95(0.01-32.00)，3.62(0.01-11.30)，0.97（0.35-14.50），3.45(0.01-19.96)/2.35(0.01-29.00)，0.45(0.01-5.56)，0.56（0.01-3.50），3.16(0.01-19.54)，the former is significant higher than the latter（P<0.05）.Theconcentration of HMGB1in BALF of patient group has linear correlation with theconcentration of IL-1β、TNF-α（r=0.685,R=0.624，P <0.05）.In patient group,theconcentration of HMGB1in BALF extracted from middle and severe patient issignificantly higher than that from gently patient（P<0.05）.Conclusions:The expression of HMGB1in BALF extracted from COPD patient issignificantly increased and correlate with the severity of disease.The concentration ofHMGB1in BALF extracted from COPD patient has significant correlation with that ofinflammatory factor such as IL-1β、TNF-α.

        高遷移率族蛋白B1在COPD病人支氣管肺泡灌洗液中的表達及其意義

目錄4-5英文縮略詞表5-7中文摘要7-8英文摘要8-10引言11-13材料與方法13-19結(jié)果19-23討論23-32結(jié)論32-33參考文獻33-41附錄41-42致謝42-43綜述43-53    參考文獻50-53

  本文關(guān)鍵詞：高遷移率族蛋白B1在COPD病人支氣管肺泡灌洗液中的表達及其意義，由筆耕文化傳播整理發(fā)布。