COPD患者TLR-4表达与气道炎症及气道粘液高分泌的研究

发布时间：2018-03-31 05:14

本文选题：肺疾病　切入点：慢性阻塞性　出处：《青岛大学》2012年硕士论文

【摘要】：目的：检测慢性阻塞性肺病患者肺组织中TLR-4, HBD-2, IL-8, MUC5AC的表达,并探讨TLR-4在气道炎症、气道粘液高分泌中的作用。方法：收集40例男性肺癌患者手术切除标本,根据肺功能结果分为COPD组(20人)及非COPD组(20人),取其肺叶切除后的远离癌变部位的肺组织,对肺组织标本行HE、AB-PAS染色,显微镜下观察肺组织基本形态结构,对气道炎症细胞进行评分,用免疫组织化学方法检测肺组织中TLR-4, IL-8, HBD-2, MUC5AC的表达并分析其相关性。结果：①COPD组出现明显气道炎症细胞浸润,COPD组气道炎症细胞评分(2.67±0.26)较对照组(1.15±0.34)增加(P0.05)。肺功能正常吸烟者与非吸烟者气道炎症细胞评分分别为(1.49±0.36,0.82±0.04),肺功能正常吸烟者气道炎症细胞评分较非吸烟者增加(P0.05), COPD组气道上皮杯状细胞百分比(27.83±6.72)较对照组(12.67±4.12)增加(P0.05)。COPD患者气道MUC5AC主要表达于气道杯状细胞,COPD组及对照组气道MUC5AC阳性率分别为(24.16±3.63) COPD组较对照组增高(16.12±4.41, P0.05).②COPD组肺组织中TLR-4、 HBD-2及IL一8表达的IOD值(分别为1110.12±302.61,1480.23±292.51,1496.41±346.86)较对照组(分别为724.21±242.13,864.31±121.53,654.46±215.16)增高(P0.05)。TLR-4主要表达在气道壁及其周围浸润的单核一巨噬细胞、中性粒细胞,气道上皮细胞、支气管平滑肌细胞、血管内皮细胞也有表达,HBD-2主要表达于气道上皮细胞,IL-8在气道壁及其周围浸润的淋巴细胞、巨噬细胞、中性粒细胞均有表达。③吸烟组气道炎症细胞评分、杯状细胞百分比、MUC5AC阳性率(分别为2.67+0.28,64.12±1.13,32.43+1.21)较非吸烟组(1.02±0.14,30.12±1.13,12.98±1.76)增高(P0.05)。④相关性分析：TLR-4表达与气道中性粒细胞百分比、IL-8及HBD-2表达成正相关(r值分别是0.81、0.92、0.80,P均0.05),TLR-4表达与气道MUC5AC表达成正相关(r为0.74,P0.05),IL-8与MUC5AC表达成正相关(r为0.82, P0.05), IL-8与气道中性粒细胞及淋巴细胞百分比成正相关(r为0.94、0.78,P0.05)。气道炎症评分、杯状细胞百分比及MUC5AC阳性率与吸烟指数呈正相关(r值分别为0.86、0.89、0.81,P0.05)。结论：COPD患者气道中TLR-4表达上调诱导HBD-2、IL-8表达增加,参与了COPD气道炎症反应,HBD-2作为TLR-4的内源性配体可导致COPD气道炎症反应放大,COPD患者MUC5AC主要由杯状细胞细胞产生,TLR-4通过间接诱导MUC5A表达参与气道粘液高分泌。
[Abstract]:Aim: to detect the expression of TLR-4, HBD-2, IL-8, MUC5AC in pulmonary tissue of patients with chronic obstructive pulmonary disease (COPD), and to investigate the role of TLR-4 in airway inflammation and airway mucus hypersecretion.Methods: 40 male patients with lung cancer were divided into COPD group (n = 20) and non-#en1# group (n = 20) according to the results of lung function.The expression of TLR-4, IL-8, HBD-2 and MUC5AC in lung tissue was detected by immunohistochemical method and the correlation was analyzed.Results the score of airway inflammatory cells in the COPD group (2.67 卤0.26) was higher than that in the control group (1.15 卤0.34).The scores of airway inflammatory cells in normal lung function smokers and non-smokers were 1.49 卤0.36 卤0.82 卤0.04g, respectively. The airway inflammatory cell score of normal smokers was higher than that of non-smokers (P 0.05). The percentage of goblet cells in airway epithelium in COPD group was 27.83 卤6.72), which was higher than that in control group (12.67 卤4.12).(724.21 卤242.13864.31 卤121.53654.46 卤215.16) the expression of P0.05U. TLR-4 was mainly expressed in mononuclear macrophages infiltrated in the airway wall and surrounding airway wall.The expression of HBD-2 in neutrophilic granulocytes, airway epithelial cells, bronchial smooth muscle cells and vascular endothelial cells was mainly expressed in lymphocytes and macrophages infiltrated in and around the airway wall of airway epithelial cells.Neutrophil expression 3. 3 in smoking group, airway inflammatory cell score,The positive correlation between IL-8 expression and MUC5AC expression was 0.82, P 0.05, and the positive correlation between IL-8 and the percentage of airway neutrophils and lymphocytes was 0.94 ~ 0.78%.Airway inflammation score, goblet cell percentage and MUC5AC positive rate were positively correlated with smoking index.Conclusion the up-regulated expression of TLR-4 induces the increase of HBD-2 IL-8 expression in the airway of patients with TLR-4.As an endogenous ligand of TLR-4, HBD-2 involved in the airway inflammation response of COPD may induce MUC5AC to produce TLR-4 mainly by goblet cells and participate in airway mucus hypersecretion through indirect induction of MUC5A expression in COPD patients.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R563.9

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