TOLL 样受体4、基质金属蛋白酶-9在慢性阻塞性肺疾病肺血管中的表达及其与肺血管重建的关系

目的：探讨TOLL样受体4（TLR4）、基质金属蛋白酶-9（MMP-9）在慢性阻塞性肺疾病肺血管中的表达及其与肺血管重建的关系。方法收集因肺鳞癌行肺叶切除的癌旁组织标本50例，根据肺功能分为COPD组和非COPD组各25例，镜下观察炎症程度及测定肺动脉管壁面积/管总面积（ WA％）、管壁厚度/血管外径（ WT％）。免疫组化法测定肺血管平滑肌细胞TLR4、MMP-9及增殖细胞核抗原（ PCNA）的表达，并分析其与血管重建的相关性。结果⑴COPD组肺血管炎症程度、WA％、WT％显著高于非COPD组，差异有统计学意义（ P ＜0.01）；⑵COPD组肺血管平滑肌细胞TLR4、MMP-9的表达水平与非COPD组相比明显升高，差异有统计学意义（ P ＜0.01）；⑶TLR4、MMP-9表达水平与WA％、WT％及血管炎症程度呈正相关（ r ＝0.67，0.74，0.47；0.59，0.71，0.61， P ＜0.01），与PCNA的表达呈正相关（ r ＝0.44，0.33， P ＜0.01），TLR4表达水平的上调与MMP-9的表达呈正相关（ r ＝0.55， P ＜0.01）。结论 COPD患者肺动脉存在明显炎症反应、血管肌化，TLR4表达的上调可能加剧炎症反应，同时促使MMP-9的表达增强，在肺血管重建过程中起到了重要作用。

Relationships between the expressions of matrix metalloproteinase-9,Toll-like Receptor 4 and lung revascularization in pa-tients with chronic obstructive pulmonary disease

Objective To explore the correlation between the expressions of matrix metalloproteinase -9 （MMP-9）, Toll-likeReceptor 4 （ TLR4） and lung revascularization in patients with chronic obstructive pulmonary disease .Methods Lung tissues frompatients with chronic obstructive pulmonary disease （COPD） （COPD group,n =25） and those without COPD （non-COPD group,n =25） were obtained from surgically resected specimens .The ratio of the area of the wall to that of the pulmonary arterioles （WA %） andthe ratio of the thickness of the wall to the external diameter of the pulmonary arterioles （WT %） were analyzed by computer-based imageanalysis system.Immunohistochemical technique was applied to investigate the expressions of TLR 4, proliferative cell nuclear antigen（PCNA） and MMP-9 in vascular smooth muscle cells.Results ⑴ The inflammatory infiltration degree, WA %, and WT %were significantly higher than that of non -COPD group （ P 〈0.01）, respectively.⑵Compared with non-COPD group, the expressionsof PCNA, TLR4, and MMP-9 in vascular smooth muscle cells were increased significantly （ P 〈0.01）.⑶The expressions of TLR4,MMP-9 had a positive correlation with WA%, WT%, degree of inflammatory infiltration, and the expression of PCNA （ r =0.67,0.74,0.47,0.44;0.59,0.71,0.61,0.33, P 〈0.01）, up-regulated expression of TLR4 was closely related with the expression of MMP-9 （ r =0.55, P 〈0.01）.Conclusions The pulmonary arterioles of COPD patients showed marked inflammatory and arteriolemuscularization, the TLR4 might aggravate inflammation,induced upregulation of MMP-9 expression, played an important role in the pulmonary vascular remodeling process.