【作者】 蔡仁萍；

【导师】 吴世满；

【作者基本信息】 山西医科大学 ， 呼吸内科学， 2010， 硕士

【摘要】 目的：探讨诱导痰中基质金属蛋白酶-9(MMP-9)及其抑制剂-1(TIMP-1)和转化生长因子-β1 (TGF-β1),高分辨CT (HRCT)和肺功能检查在评价支气管哮喘(简称哮喘)患者气道重塑方面的作用。方法：2008年6月至12月就诊于山西医科大学第一医院的哮喘患者48例,根据应用β2-受体激动剂后是否出现气流可逆,将哮喘患者分为可逆气流阻塞组(24例)和不可逆气流阻塞组(24例),以及对照组(10名)。通过盐水诱导痰液,利用ELISA方法检测哮喘患者及对照者诱导痰中的MMP-9、TIMP-1和TGF-β1浓度。同时所有入选者进行常规肺功能及肺部HRCT检查,测定肺部HRCT的气道壁厚度与外径比值2倍的百分比(2T/D)和气道壁面积占气道总截面积百分比(WA%)。结果：1.不可逆气流阻塞组和可逆气流阻塞组诱导痰中的MMP-9, TIMP-1和TGF-β1含量均高于对照组(P均<0.05),不可逆气流阻塞组含量均高于可逆气流阻塞组(P均<0.05)；不可逆气流阻塞组和可逆气流阻塞组MMP-9/TIMP-1比值均低于对照组(P均<0.05),不可逆气流阻塞组MMP-9/TIMP-1比值低于可逆气流阻塞组(P<0.05)。2.不可逆气流阻塞组和可逆气流阻塞组2T/D、WA%值高于对照组(P均<0.05)；不可逆气流阻塞组值高于可逆气流阻塞组(P<0.05)。3.诱导痰中MMP-9与2T/D、WA%呈正相关(r=0.755、0.751,P均< 0.05); TIMP-1与2T/D、WA%呈正相关(r=0.639、0.630,P均<0.05);TGF-β1与2T/D、WA%亦呈正相关(r=0.872、0.868,P均<0.05)。4.诱导痰中MMP-9、TIMP-1、TGF-β1,2T/D, WA%与肺功能FEV1%均呈负相关(r=-0.496、-0.468、-0.607、-0.599、-0.586,P均<0.05)；其与肺功能FVC%均呈负相关(r=-0.312、-0.359、-0.399、-0.407、-0.388,P均<0.05)；其与肺功能FEF25-75%亦均呈负相关(r=-0.558、-0.477、-0.649、-0.645、-0.651,P均<0.05)。结论：1. HRCT可作为无创手段评估哮喘患者气道重塑情况。2.诱导痰中MMP-9、TIMP-1和TGF-β1可以作为气道重塑的生物标记物。3.诱导痰中MMP-9、TIMP-1、TGF-β1和HRCT能较早地发现气道重塑,其有可能指导临床早期治疗哮喘并监测治疗效果。4.采用诱导痰的方法获取气道信息是一种安全有效的方法。更多还原

【Abstract】 Objective:To explore the roles of biomarkers of MMP-9,TIMP-1 and TGF-β1 in induced sputum,high-resolution CT and pulmonary function in assessing airway remodeling in asthma.Method:Forty-eight patients with asthma were chosen in the first hospital of Shanxi medical university from June to December 2008. According whether airflow obstruction was reversible or not being used p2-receptor agonists,they were divided into two groups:irreversible airflow obstruction group and reversible airflow obstruction one,and 24 patients each group,and control group included 10 persons.The sputum was induced with Saline,and the MMP-9,TIMP-1 and TGF-β1 level of the sputum were determined with ELISA.All selected persons over the same period did pulmonary function and HRCT tests.The wall thickness two-fold to airway diameter ratio(2T/D) and the percentage of airway wall area to total airway cross sectional area(WA%) were calculated on high resolution computed tomography.Result:(1) The levels of MMP-9, TIMP-1 and TGF-β1 in asthma group were higher than those in the controlled group (P＜0.05) respectively;and those in the irreversible airflow obstruction group were higher than ones in the reversible airflow obstruction group (P＜0.05) respectively.The MMP-9/TIMP-1 ratio in asthma group was lower than in control group (P＜0.05);and the irreversible airflow obstruction group was lower than the reversible airflow obstruction group,(P＜0.05).(2) 2T/D and WA%were higher in asthma group than in control group (P＜0.05) respectively;and the irreversible airflow obstruction group was higher than the reversible airflow obstruction group,(P＜0.05).(3) The MMP-9 level of induced sputum was positively correlated with 2T/D and WA%(r=0.755,0.751,P＜0.05);The TIMP-1 level was positively correlated with 2T/D and WA%(r=0.639,0.630,P＜0.05);The TGF-β1 level was also positively correlated with 2T/D and WA%(r=0.872,0.868,P＜0.05).(4) MMP-9, TIMP-1, TGF-β1,2T/D and WA%were negatively correlated with FEV1%(r=-0.496,-0.468,-0.607,-0.599,-0.586,P＜0.05);those were negatively correlated with FVC%(r=0.312、-0.359、-0.399、-0.407、-0.388,P＜0.05);those were also negatively correlated with FEF25-75%(r=-0.558、-0.477、-0.649、-0.645、-0.651,P＜0.05)Conclusion:(1) The airway remodeling can be assessed by HRCT.(2) MMP-9, TIMP-1 and TGF-β1 in induced sputum could be as biomarkers as airway remodeling in asthma. (3) MMP-9,TIMP-1,TGF-β1 in induced sputum and HRCT could find airway remodeling earlier,which may be guiding clinical treatment and monitoring therapeutic effect. (4) It was a safe and effective way that airway secretions were obtained through the induced sputum.更多还原