高迁移率族蛋白B1在COPD病人支气管肺泡灌洗液中的表达及其意义

  本文关键词：高迁移率族蛋白B1在COPD病人支气管肺泡灌洗液中的表达及其意义，由笔耕文化传播整理发布。

        研究背景：慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）是一种全球性患病率和死亡率很高而病因及发病机制尚不完全清楚的疾病。COPD主要累及肺脏，但也可引起全身的不良效应。COPD特征性的病理改变存在于中央气道、外周气道、肺实质和肺血管系统。病理改变包括慢性炎症，，表现为肺组织不同部位特定的炎症细胞增加，以及由于反复损伤和修复引起的结构变化，即气道重塑。COPD的发病机制尚未完全明了。目前普遍认为是蛋白酶-抗蛋白酶失衡、氧化-抗氧化失衡及气道慢性炎症等因素共同作用的结果。炎症在COPD的发病机制中处于中心地位。现已明确多种炎症细胞和气道结构细胞以及其分泌的多种炎症介质参与慢性气道炎症、气道重塑的发生发展。高迁移率族蛋白B1（highmobility group box-1protein,HMGB1）是一种普遍存在的高度保守的核蛋白，参与DNA的转录、复制、修复以及炎症反应等。目前相关研究表明，HMGB1在COPD的发病机制中扮演着重要角色。在COPD病人气道中，气道炎症细胞如巨噬细胞，单核细胞和气道结构细胞如上皮细胞，平滑肌细胞高水平表达并分泌HMGB1，而HMGB1又可促进其他致炎症细胞因子的释放，促进气道炎症的发生。本研究提取COPD患者的支气管肺泡灌洗液并分析灌洗液中HMGB1的含量及其他炎症因子的含量，初步探讨HMGB1在COPD中的作用。目的：通过测定COPD患者的支气管肺泡灌洗液中HMGB1的含量，初步探讨HMGB1在COPD气道炎症中的作用。方法：将研究对象分为疾病组和对照组，分别行支气管镜检查并支气管肺泡灌洗术，提取支气管肺泡灌洗液。分析两组灌洗液的细胞计数及分类，用酶联免疫吸附法测定（ELISA）测定HMGB1，IL-1β，IL-8及TNF-α的含量，分析HMGB1和其他炎症因子间的关系，并分析HMGB1和疾病严重程度间的关系。结果：对照组和COPD组BALF（支气管肺泡灌洗液）中的细胞总数、单核巨噬细胞及中性粒细胞百分比分别为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)%。和对照组相比，COPD组BALF的细胞总数、中性粒细胞百分比较高，二者有显著性差异(P <0.05)，而单核巨噬细胞较低，二者有显著性差异(P <0.05)。对照组和COPD组BALF中的淋巴细胞百分分别为2.4（3.6-8.6）%、2.7(4.3-9.7)%，两组差异无统计学意义（p＞0.05）。COPD组和对照组BALF中HMGB1(ug/L)、IL-1β（ng/L），TNF-α（ng/L）及IL-8（ng/L）的含量分别为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组HMGB1, IL-1β, TNF-α显著高于对照组（P<0.05），且HMGB1的含量和IL-1β、TNF-α呈线性相关（r=0.685及0.624，P均<0.05）。在COPD组中，中重度病人BALF中HMGB1含量显著高于轻度病人（P<0.05）。结论：COPD病人支气管肺泡灌洗液中HMGB1的表达明显增高，与疾病的严重程度具有一定的关联性。支气管肺泡灌洗液中HMGB1的含量和IL-1β、TNF-α等炎症因子的含量具有显著相关性。

    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.

        高迁移率族蛋白B1在COPD病人支气管肺泡灌洗液中的表达及其意义

目录4-5英文缩略词表5-7中文摘要7-8英文摘要8-10引言11-13材料与方法13-19结果19-23讨论23-32结论32-33参考文献33-41附录41-42致谢42-43综述43-53    参考文献50-53

  本文关键词：高迁移率族蛋白B1在COPD病人支气管肺泡灌洗液中的表达及其意义，由笔耕文化传播整理发布。