【作者】 李海燕；

【导师】 于文成；

【作者基本信息】 青岛大学 ， 内科学， 2009， 硕士

【摘要】 目的:通过对慢性阻塞性肺疾病(COPD)患者肺组织标本中肺血管内皮细胞过氧化物酶体增殖激活受体γ(peroxisome proliferators activated receptor gamma,PPARγ)和金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达的研究,探讨PPARγ、MMP-9在慢性阻塞性肺疾病肺血管炎症和肺血管重塑中的作用。方法:收集在我院胸外科住院,需要手术治疗且有吸烟史的男性鳞癌患者的临床资料及正常肺组织。按其肺功能结果将30例病人分成二组,对照组:(肺功能正常组);COPD组:(COPD稳定期组),每组15例。均于术前行肺功能检查和心脏超声检查根据三尖瓣反流压差估测肺动脉收缩压(PASP),记录吸烟指数,入选患者无其他肺部疾病及其他系统慢性病变,取其肺叶切除后无癌细胞浸润的外周肺组织,行苏木精一伊红(HE)染色,光镜下观察肺组织基本结构,并行维多利亚蓝+立春红S染色,计算肺腺泡内肌化动脉、部分肌化动脉、非肌化动脉数目,图像分析观察及测定肺小动脉管壁面积/血管总面积、管腔面积/血管总面积、内膜面积/血管总面积及血管旁胶原纤维面积。应用免疫组织化学方法检测肺血管内皮细胞PPARγ、MMP-9表达,并进行相关分析。结果:1)正常的肺血管内皮细胞表达PPARγ,COPD组肺血管内皮细胞所含PPARγ的阳性标记物百分比(2.65%±0.89%)低于对照组(12.28%±4.23%)(P<0.01),所含MMP-9的阳性标记物百分比(38.53%±11.73%)高于对照组(12.83%±3.89%)。2)COPD组与对照组比较,肺功能明显下降,符合COPD诊断标准。3)肺腺泡内动脉病理图像分析:与对照组比较,COPD组病人肺小动脉管壁充血水肿,炎性细胞浸润增多,管腔面积减小,内膜面积、管壁面积与血管总面积之比值增大,血管旁胶原纤维面积增加。4)相关分析:肺血管内皮细胞PPARγ表达与MMP-9表达呈负相关(r=-0.85,P<0.01),与炎性细胞及肺小动脉肌化动脉比例、部分肌化动脉比例、血管旁胶原纤维面积成负相关(r分别=-0.604、-0.759、-0.485、-0.86,P值均<0.01);MMP-9表达与炎性细胞及肺小动脉肌化动脉比例、部分肌化动脉比例、血管旁胶原纤维面积成正相关(r分别=0.524、0.961、0.574、0.954,P值均<0.01);血管管壁面积和血管旁胶原纤维面积呈正相关(r=0.878,P<0.01);所有吸烟者的吸烟指数与肺小动脉肌化动脉比例、部分肌化动脉比例成正相关(r分别=0.889、0.764,P值均<0.01)。结论:吸烟者和慢性阻塞性肺病患者均存在不同程度的肺血管炎症反应和肺血管重塑,在此过程中,MMP-9促进炎症反应,参与肺血管重塑过程,而PPARγ改善炎症反应,发挥抗重塑的作用。更多还原

【Abstract】 Objective:In order to investigate the effect of peroxisome proliferators activated receptor gamma and matrix metalloproteinase-9 in pulmonary vascular inflammation and remodeling in patients with chronic obstructive pulmonary disease(COPD) by detecting the expression of PPARγand MMP-9 of pulmonary vascular endothelial cells.Methods:Lung specimens were collected from the male patients who with lung carcinoma and smoking history and need to be operated in thoracic surgery,30 patients were divided into 2 groups, control group:patients with normal pulmonary function(non-COPD group) and patients with COPD (COPD group),each of 15 cases,matched with age.Air flow obstruction was determined by pulmonary function test and pulmonary artery pressure were examined by continuous wave Doppler echocardiographic measurement of the tricuspid regurgitant jet,and the smoking index were recorded in all patients before the operations.The remodeling of pulmonary artery remodeling was observed with HE staining under microscope and triple strains,lumen area,arteries walls,intimal area,muscular arteries,partial muscular arteries,non partial muscular arteries were measured,the expression of PPARγand MMP-9 of pulmonary vascular endothelial cells were measured by means of immunohisto-chemistry,analysis were made.Results:1) Normal pulmonary vascular endothelial cells express PPARγ,the expression of PPARγin control group(12.28%±4.23%) was higher than that in COPD group(2.65%±0.89%)(P <0.01 ),and the expression of MMP-9 in COPD group(38.53%±11.73%)was higher than that in control group(12.83%±3.89%).2) Pulmonary function in COPD group drops compared with control group.3) Characteristics of intra-acinar pulmonary muscular arteries:Compared with control group, arteries walls of COPD group congested and swelled,inflammation cells increased,the thickness of intimal layer、walls of intra-acinar pulmonary muscular arteries was significantly higher,the area of its lumen was narrow and the proportion of their muscular arteries was higher,the area of collagen fibrils was increased.4) Correlation analysis:An negative correlations were showed with the expression of PPARγand MMP-9(r = -0.85,p<0.01 ),and inflammation cells,the pulmonary artery of the artery muscle ratio,the area of collagen fibrils,negative correlation was showed(r=-0.604、-0.759、-0.485、-0.862,P< 0.01);An positive correlations were showed in the expression of MMP-9 and inflammation cells(r=0.524,P<0.01 ),an positive correlation was showed with the pulmonary artery of the artery muscle ratio,the area of collagen fibrils,(r= 0.961、0.574、0.954,P<0.01);the artery wall area and the area of collagen fibrils showed positive correlations(r = 0.878,p< 0.01).an positive correlation was showed with the smoking index and the ratio of muscular arteries,partial muscular arteries,the area of collagen flbrils(r=0.889、0.764,P<0.01).Conclusion:Patients with smoking and COPD have pulmonary vascular inflammation and remodeling,MMP-9 of pulmonary vascular endothelial cells was involved in the inflammation and remodeling process.,but PPARγwas involved in the anti-inflammation and anti-remodeling process.更多还原