發(fā)布時(shí)間：2018-05-25 05:16

  本文選題：慢性阻塞性肺疾病 + 肺間質(zhì)　； 參考：《天津醫(yī)科大學(xué)》2017年碩士論文

【摘要】：研究目的:探討慢性阻塞性肺疾病(COPD)患者肺間質(zhì)中肺泡隔的病理學(xué)改變及其與氣流受限之間的關(guān)系。研究方法:采用單中心前瞻性研究方法,分析我院因肺部良惡性腫瘤行肺葉切除手術(shù)患者術(shù)后病理標(biāo)本。根據(jù)納入標(biāo)準(zhǔn)選擇病例,并根據(jù)肺功能(FEV1/FVC%)將病例分為COPD組和正常對照組。術(shù)后病理標(biāo)本選取距腫瘤部位大于2cm的胸膜下肺組織。行蘇木精-伊紅(HE)染色觀察肺組織形態(tài)及肺泡隔厚度;Elastica Van Gieson(EVG)染色觀察肺泡隔中彈力纖維和膠原纖維比例;免疫組化染色分析肺泡隔基質(zhì)金屬蛋白酶-2(MMP-2)、基質(zhì)金屬蛋白酶-9(MMP-2)、金屬蛋白酶組織抑制因子-1(TIMP-1)表達(dá)水平。以第1秒用力呼氣容積占預(yù)計(jì)值百分比(FEV1%pred)表示COPD氣流受限嚴(yán)重程度并對COPD組患者進(jìn)行嚴(yán)重程度分級(jí)。比較2組間及不同嚴(yán)重程度COPD組間肺間質(zhì)中肺泡隔病理變化,并觀察肺泡隔病理改變與FEV1%Pred、一氧化碳彌散量占預(yù)計(jì)值百分比(DLco%Pred)的關(guān)系以及肺泡隔病理改變與MMP-2,MMP-9及TIMP-1之間的關(guān)系。研究結(jié)果:1、共有60例患者納入研究,其中COPD組40例,對照組20例。2組間性別、年齡、吸煙指數(shù),標(biāo)本獲取部位比較無顯著性差異(P0.05),重度COPD組DLco%Pred為61.51±12.83較輕、中度COPD組及對照組減低(P0.05)。2、COPD組鏡下可見肺泡隔中纖維排列紊亂,肺泡隔斷裂明顯增多,肺泡腔擴(kuò)張。3、COPD組肺泡隔厚度6.9±2.11um,肺泡隔中膠原纖維占47.6±12.62%較對照組增高;彈力纖維占37.43±12.96%,彈力纖維/膠原纖維為82.87±38.85%較對照組減低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。在COPD組中,重度COPD組肺泡隔厚度9.00±2.39um,膠原纖維占59.5±13.52%,較輕、中度COPD組增加,重度COPD患者彈力纖維占27.88%,彈力纖維/膠原纖維為48.38±17.97%較輕、中度COPD組減低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。4、肺泡隔病理改變與肺功能關(guān)系:(1)肺泡隔厚度、膠原纖維所占比例與FEV1%pred呈負(fù)相關(guān)(r值分別為-0.335、-0.472;p值分別為0.035、0.002),彈力纖維所占比例及彈力纖維/膠原纖維與FEV1%pred呈正相關(guān)(r值分別為0.316、0.522;P值分別為0.047、0.001);(2)肺泡隔膠原纖維所占比例與DLco%pred呈負(fù)相關(guān)(r-0.329,P=0.010),彈力纖維所占比例及彈力纖維/膠原纖維與DLco%pred呈正相關(guān)(r值分別為0.316、0.452;P值分別為0.014、0.000)。5、COPD組肺泡隔MMP-2、MMP-9、TIMP-1表達(dá)較對照組增加,差異有統(tǒng)計(jì)學(xué)意義(P0.05);COPD組中,重度COPD患者肺泡隔中MMP-2、MMP-9、TIMP-1表達(dá)較輕、中度COPD組增高,而MMP-2/TIMP-1、MMP-9/TIMP-1較輕、中度COPD組減低,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:COPD患者肺間質(zhì)中肺泡隔纖維排列紊亂,肺泡隔斷裂增多;COPD患者肺泡隔厚度增加,膠原纖維比例增多,彈力纖維比例減少。其中重度COPD組患者與輕、中度COPD患者比較肺泡隔病理變化更加明顯。肺泡隔厚度及肺泡隔中膠原纖維比例與FEV1%pred呈負(fù)相關(guān),而肺泡隔中彈力纖維比例及彈力纖維/膠原纖維與FEV1%pred呈正相關(guān);肺泡隔膠原纖維比例與DLco%pred呈負(fù)相關(guān),彈力纖維所占比例及彈力纖維/膠原纖維與DLco%pred呈正相關(guān)。COPD患者肺泡隔中MMP-2、MMP-9、TIMP-1表達(dá)增加,重度COPD患者較輕、中度COPD患者此種表現(xiàn)更加明顯,并且重度COPD患者M(jìn)MP-2/TIMP-1、MMP-9/TIMP-1較輕、中度COPD組減低。說明COPD患者肺泡隔病理學(xué)改變與其肺功能變化相關(guān),MMP-2、MMP-9、TIMP-1表達(dá)及其比例變化在肺泡隔病理改變中起到重要作用。
[Abstract]:Objective: To investigate the pathological changes of pulmonary alveolar septum in the pulmonary interstitial tissue of patients with chronic obstructive pulmonary disease (COPD) and the relationship between the pulmonary alveolar septum and the airflow limitation. Methods: a single center prospective study was used to analyze the pathological specimens of patients with pulmonary benign and malignant tumors undergoing lobectomy. The cases were divided into COPD group and normal control group according to the pulmonary function (FEV1/FVC%). The pathological specimens were selected from the lower pleural tissue of the tumor larger than 2cm. The pulmonary tissue morphology and alveolar septum thickness were observed by hematoxylin eosin (HE) staining. The proportion of elastic and collagen fibers in the alveolar septum was observed by Elastica Van Gieson (EVG) staining; the immunological group was observed. Pulmonary alveolar matrix metalloproteinase -2 (MMP-2), matrix metalloproteinase -9 (MMP-2), and tissue inhibitor of metalloproteinase -1 (TIMP-1) expression level were analyzed by chemical staining. The percentage of forced expiratory volume (FEV1%pred) in the 1st second (FEV1%pred) expressed the severity of COPD airflow limitation and graded the severity of the patients in the COPD group. The comparison between the 2 groups was compared. The pathological changes of alveolar septum in the pulmonary interstitium with the COPD group, and the relationship between the pathological changes of the alveolar septum and FEV1%Pred, the percentage of the estimated carbon monoxide dispersion (DLco%Pred) and the relationship between the pathological changes of the alveolar septum and the MMP-2, MMP-9 and TIMP-1. The results were as follows: 1, 60 patients were included in the study, of which 40 cases were in group COPD. There was no significant difference in the sex, age, smoking index between the 20.2 groups, the DLco%Pred in the severe COPD group was 61.51 + 12.83, the moderate COPD group and the control group decreased (P0.05).2. The fiber arrangement disorder in the alveolar septum, the alveolar septum dilation and the alveolar septum thickness in the pulmonary alveolus were found in the COPD group. 6.9 + 2.11um, the collagen fiber in the alveolar septum was 47.6 + 12.62% higher than the control group, the elastic fiber was 37.43 + 12.96%, the elastic fiber / collagen fiber was 82.87 + 38.85% lower than the control group. The difference was statistically significant (P0.05). In the group COPD, the thickness of the alveolar septum was 9 + 2.39um, the collagen fibers accounted for 59.5 + 13.52%, and the moderate COPD group increased. Plus, the elastic fiber of severe COPD patients was 27.88%, elastic fiber / collagen fiber was 48.38 + 17.97% light, and the moderate COPD group decreased. The difference was statistically significant (P0.05).4. The relationship between pulmonary alveolar septum pathological changes and pulmonary function was (1) the thickness of alveolar septum, the proportion of collagen fiber was negatively correlated with FEV1%pred (r value was -0.335, -0.472, P value respectively 0.035,0, respectively, 0.035,0. .002), the proportion of elastic fibers and elastic fiber / collagen fibers were positively correlated with FEV1%pred (r value was 0.316,0.522, P was 0.047,0.001 respectively); (2) the proportion of collagen fibers in alveolar septum was negatively correlated with DLco%pred (r-0.329, P=0.010), the proportion of elastic fibers and elastic fiber / collagen fibers were positively correlated with DLco%pred (r value, respectively) 0.316,0.452, P value was 0.014,0.000).5, COPD group alveolar septum MMP-2, MMP-9, TIMP-1 expression increased compared with the control group, the difference was statistically significant (P0.05). Significance (P0.05). Conclusion: pulmonary alveolar septum fibers in the pulmonary interstitium of COPD patients were in disorder, alveolar septum fracture increased, alveolar septum thickness increased in COPD patients, the proportion of collagen fibers increased, and the proportion of elastic fibers decreased. The pathological changes of alveolar septum in patients with severe and moderate COPD were more obvious. The thickness of alveolar septum and collagen in the alveolar septum were more obvious in patients with severe COPD. The ratio of fiber to FEV1%pred was negatively correlated, and the elastic fiber ratio in the alveolar septum and the elastic fiber / collagen fiber were positively correlated with the FEV1%pred; the proportion of collagen fibers in the alveolar septum was negatively correlated with DLco%pred, the proportion of elastic fibers and the elastic fiber / collagen fiber and MMP-2, MMP-9, TIMP-1 expression in the alveolar septum of DLco%pred Cheng Zhengxiang patients with.COPD. In patients with severe COPD, severe and moderate COPD patients had more obvious performance, and severe COPD patients were MMP-2/TIMP-1, MMP-9/TIMP-1 was lighter, and moderate COPD decreased. The pathological changes of alveolar septum in COPD patients were related to changes in pulmonary function, and the changes in MMP-2, MMP-9, TIMP-1 expression and the proportion of TIMP-1 were important in the pathological changes of alveolar septum. Use.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R563.9

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