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目的探讨PPARγ、MMP-9在慢性阻塞性肺疾病(COPD)患者肺血管炎症和肺血管重塑中的作用。方法收集手术切除有吸烟史的男性鳞癌患者的肺组织。按其肺功能将30例患者分成对照组和COPD组,每组15例。术前行肺功能检查和心脏超声检查估测肺动脉收缩压(PASP),取无癌细胞浸润的外周肺组织应用HE染色和多利亚蓝-立春红S染色及图像分析,检测肺小动脉管壁面积/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)与对照组比较,COPD组肺小动脉管壁充血水肿,炎性细胞浸润明显增多,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。(2)COPD组肺血管内皮细胞PPARγ表达水平显著低于对照组(P<0.01),MMP-9的表达水平显著高于对照组(P<0.01)。(3)相关分析显示肺血管内皮细胞PPARγ表达与MMP-9表达呈负相关(r=-0.85,P<0.01);PPARγ表达与炎性细胞及肺小动脉肌化动脉比例、血管旁胶原纤维面积成负相关(r分别=-0.604、-0.759、-0.862,P<0.01);MMP-9表达与炎性细胞及肺小动脉肌化动脉比例、血管旁胶原纤维面积成正相关(r分别=0.524、0.961、0.954,P<0.01);吸烟指数与肺小动脉肌化动脉比例成正相关(r=0.889,P<0.01)。结论吸烟者和COPD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可能通过加剧肺血管炎症反应,促使血管壁细胞外基质的代谢紊乱,参与肺血管重塑过程,PPARγ可能通过抵抗炎症反应,减轻血管损伤,从而发挥抗重塑的作用。
Objective To investigate the role of PPARγ and MMP-9 in pulmonary vascular inflammation and pulmonary vascular remodeling in patients with chronic obstructive pulmonary disease (COPD). Methods Lung tissues of male patients with squamous cell carcinoma who underwent surgical resection of a smoking history were collected. According to their lung function, 30 patients were divided into control group and COPD group, 15 cases in each group. Preoperative pulmonary function tests and echocardiography were used to assess the pulmonary artery systolic pressure (PASP). Peripheral lung tissues without cancer cell infiltration were examined by HE staining and Dorothy blue-euchromatic S staining and image analysis. Area / total area of blood vessels, luminal area / total area of blood vessels, intima area / total area of blood vessels and area of peritubular collagen fibers. Immunohistochemistry was used to detect the expression of PPARγ and MMP-9 in pulmonary vascular endothelial cells, and the correlation was analyzed. Results (1) Compared with the control group, the congestion and edema of pulmonary arterioles, infiltration of inflammatory cells and the reduction of luminal area in COPD group were found. The ratio of intima area, wall area and total blood vessel area increased, Collagen fiber area increased. (2) The expression of PPARγ in pulmonary vascular endothelial cells of COPD group was significantly lower than that of control group (P <0.01), and the expression of MMP-9 was significantly higher than that of control group (P <0.01). (3) Correlation analysis showed that there was a negative correlation between the expression of PPARγ and the expression of MMP-9 in pulmonary vascular endothelial cells (r = -0.85, P <0.01); the expression of PPARγ was positively correlated with the ratio of inflammatory cells and arterial arteries in pulmonary arterioles, (R = -0.604, -0.759, -0.862, P <0.01, respectively). There was a positive correlation between the expression of MMP-9 and the percentage of arterial arteries and the area of paravertebral fibrosis (r = 0.524,0.961,0.954, P <0.01). The smoking index was positively correlated with the ratio of arterial arteries in pulmonary arterioles (r = 0.889, P <0.01). Conclusion Both smokers and COPD patients have pulmonary vascular inflammation and pulmonary vascular remodeling to varying degrees. In the process, MMP-9 may promote the metabolism of extracellular matrix of blood vessel wall through the aggravation of pulmonary vascular inflammation, Remodeling process, PPARγ may play an anti-remodeling role by resisting inflammatory reactions and reducing vascular damage.