FSTL1与支气管哮喘气道重塑的相关性研究

发布时间：2018-03-15 23:00

本文选题：FSTL1　切入点：哮喘　出处：《山东大学》2017年硕士论文　论文类型：学位论文

【摘要】：研究背景支气管哮喘(简称哮喘)是一种异质性疾病,目前认为是由炎性细胞和气道结构细胞以及多种细胞因子共同参与的慢性气道炎症性疾病。支气管哮喘的三个主要病理特征包括气道慢性炎症、气道平滑肌功能异常和气道重塑。气道重塑是指发生在气道的结构改变,包括上皮化生、杯状细胞增生、黏液分泌增加、平滑肌层增厚、上皮下纤维化、血管生成等。这些重塑的病理改变能够引起气道高反应性、气道水肿、黏液过度分泌、气道壁增厚和气道狭窄等,并导致不良临床转归。多种细胞因子在哮喘的发病以及气道重塑的过程中发挥重要作用。卵泡抑素样蛋白1(follistatin-likeprotein,FSTL1)是一种由308个氨基酸构成的分泌型糖蛋白,可由全身各系统多种细胞分泌,并具有多种生物学功能。目前FSTL1的作用机制并不明确,有研究发现其与呼吸系统发育相关,并参与呼吸系统疾病的发生和发展。研究目的对比支气管哮喘患者与正常人血浆和气道上皮组织中FSTL1水平差异。通过对比哮喘患者血浆与肺泡灌洗液(Bronchoalveolar lavage fluid,BALF)中FSTL1水平,分析血浆中FSTL1与肺泡灌洗液中FSTL1水平的相关性。分析血浆中FSTL1水平与肺功能、血常规等临床参数的相关性。分析血浆和肺泡灌洗液中FSTL1水平与气道重塑各指标之间的相关性。探讨FSTL1在支气管哮喘以及气道重塑中的作用、可能机制以及临床意义。研究方法选取来我院就诊的32名支气管哮喘患者为实验组(n=32)。另外选取前来我院常规体检的健康成人为对照组(n=25)。其中15位哮喘患者接受纤维支气管镜检查、肺泡灌洗留取肺泡灌洗液以及支气管镜活组织检查。所有受试者首诊及复诊时都经过血常规及肺功能检查并留取2ml外周血标本。采用酶联免疫吸附测定法(ELISA)检测受试者血浆和肺泡灌洗液中FSTL1水平,HE染色观察气道粘膜的基本病理改变,六胺银染色(Peridic acid silver methenamine,PASM)观察气道上皮下网状基底膜变化,天狼星红染色观察气道周围纤维化程度,采用免疫组织化学染色法检测气道上皮组织中的FSTL1的表达水平以及平滑肌肌动蛋白α(α-smoothmuscleactin,α-SMA)和I型胶原等气道重塑标记物的表达情况,利用斯皮尔曼等级相关性分析,评估血浆或肺泡灌洗液中FSTL1水平与气道重塑指标以及其他临床参数相关性。研究结果哮喘组患者血浆中的FSTL1水平(130.762±46.029ng/ml)明显高于对照组(95.408±33.938 ng/ml)(p=0.009)。哮喘患者肺泡灌洗液中的FSTL1水平与血浆中呈正相关(rs=0.550,p=0.043)。免疫组织化学染色结果显示FSTL1主要表达在上皮和间质中,哮喘组患者气道组织中FSTL1的表达量明显高于对照组,肺泡灌洗液中FSTL1的水平与气道上皮组织中Ⅰ型胶原(rs=0.779,p=0.001)、α-SMA(rs=0.561,p=0.029)、气道周围纤维化程度(rs=0.779,p=0.001)以及基底膜厚度(rs=0.660,p=0.007)具有相关性。治疗1月后,哮喘患者外周血中FSTL1水平明显下降。研究结论哮喘患者血浆及肺组织内FSTL1高表达与气道平滑肌增生和基底膜增厚密切相关。FSTL1在哮喘患者气道重塑的发展中可能发挥着重要作用。
[Abstract]:Background: bronchial asthma (asthma) is a heterogeneous disease, it is a chronic inflammatory disease by the participation of inflammatory cells and airway structural cells and cytokines. Three main pathological features of bronchial asthma including chronic airway inflammation, airway smooth muscle dysfunction and airway remodeling of airway remodeling is. The structural changes that occur in the airway, including metaplasia of goblet cell hyperplasia, increased mucus secretion, smooth muscle layer thickening, subepithelial fibrosis, angiogenesis and other pathological changes. These remodeling can cause airway hyperresponsiveness, airway edema, mucus hypersecretion, airway wall thickening and airway stenosis, and lead to adverse clinical the outcome. A variety of cytokines play an important role in the pathogenesis of asthma and airway remodeling. Follistatin like protein 1 (follistatin-likeprotein, FSTL1) is A 308 amino acid secreted glycoprotein secreted by many cells in all parts of the body, and has a variety of biological functions. The mechanism of FSTL1 is not clear, studies have found that the respiratory system development, and participate in the occurrence and development of respiratory system disease. Objective to study and compare the differences in the level of FSTL1 in patients with bronchial asthma with normal human plasma and airway epithelial tissue. By comparing the plasma and bronchoalveolar lavage fluid in patients with asthma (Bronchoalveolar lavage, fluid, BALF) in the FSTL1 level, correlation analysis of FSTL1 in plasma and alveolar lavage fluid of FSTL1 level. The analysis of FSTL1 level and lung function in plasma, blood and other clinical parameters. The correlation analysis of plasma and lung the correlation between the level of FSTL1 in the irrigation fluid and airway remodeling indexes. To investigate the FSTL1 in bronchial asthma and airway remodeling, can machine Preparation and clinical significance. Methods: 32 patients with bronchial asthma in our hospital as the experimental group (n=32). In addition to routine physical examination of healthy adults were selected in our hospital as the control group (n=25). Among the 15 patients with asthma underwent fiberoptic bronchoscopy and bronchoalveolar lavage specimens from bronchoalveolar lavage fluid and bronchoscopy live check the organization. All the subjects were first diagnosed and referral through blood and pulmonary function examination and take the 2ml. Peripheral blood samples were measured by enzyme-linked immunosorbent assay (ELISA) test subjects and plasma FSTL1 levels in the bronchoalveolar lavage fluid, HE staining pathological changes in airway mucosa, six silver amine staining (Peridic acid silver methenamine, PASM) changes of subcutaneous reticular basement membrane airway, Sirius red staining was around the airway fibrosis were detected by immunohistochemistry FSTL1 in airway epithelial tissue The expression of alpha smooth muscle actin (alpha -smoothmuscleactin, alpha -SMA) and the expression of type I collagen and airway remodeling markers, using Spielman correlation analysis, evaluation of plasma and bronchoalveolar lavage fluid in FSTL1 level and airway remodeling index and other clinical parameters. The results of correlation between asthma patients plasma FSTL1 levels (130.762 + 46.029ng/ml) was significantly higher than the control group (95.408 + 33.938 ng/ml) (p=0.009). The alveolar asthma patients was positively correlated with plasma FSTL1 levels and irrigation lotion in (rs=0.550, p=0.043). Immunohistochemical staining results showed that FSTL1 mainly expressed in the epithelium and stroma, expression of FSTL1 in asthma airway tissues significantly higher than the control group, type I alveolar lavage lotion FSTL1 level and airway epithelial tissue collagen (rs=0.779, p=0.001), alpha -SMA (rs= 0.561, p=0.029), airway fiber The dimension degree (rs=0.779, p=0.001) and basement membrane thickness (rs=0.660, p=0.007) with correlation. After treatment in January, FSTL1 level in peripheral blood of patients with asthma decreased obviously. Conclusions patients with asthma in plasma and lung tissue FSTL1 expression and airway smooth muscle hyperplasia and thickening of the basement membrane is closely related to.FSTL1 may play an important role in the development of airway remodeling in asthma.

【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R562.25

【相似文献】