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目的探讨慢性阻塞性肺疾病患者肺血管中基质金属蛋白酶-9(MMP-9)及其组织金属蛋白酶抑制剂-1(TIMP-1)的表达与肺血管重建的关系及临床意义。方法取60例因肺鳞癌行肺叶切除的癌旁组织标本,其中慢性阻塞性肺疾病组30例和对照组30例,图像分析系统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MMP-9、TIMP及平滑肌细胞增殖细胞核抗原(PCNA)表达,并分析其与血管重建相关性。结果 (1)慢性阻塞性肺疾病组肺血管炎症程度、WA%、WT%显著高于对照组(P<0.01)。(2)肺血管平滑肌细胞PCNA、MMP-9、TIMP-1的表达水平与对照组相比明显升高(P<0.01)。(3)相关分析:慢性阻塞性肺疾病组MMP-9、TIMP-1表达水平与血管炎症程度、WA%、WT%及PCNA呈显著正相关(P<0.01),多重线性回归分析显示MMP-9、TIMP-1表达水平的上调是影响肺血管重建(WA%、WT%)的主要因素(P<0.01)。结论 MMP-9、TIMP-1表达增强引起细胞外基质异常降解,诱导平滑肌增殖,促进炎症细胞迁移,在肺血管重塑过程中起到了重要作用。
Objective To investigate the relationship between the expression of matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and pulmonary vascular remodeling in patients with chronic obstructive pulmonary disease and its clinical significance. Methods Sixty patients with lung squamous cell carcinoma underwent lobectomy were divided into three groups: 30 cases of chronic obstructive pulmonary disease group and 30 cases of control group. The pulmonary artery wall area and total tube area (WA%) were determined by image analysis system. Wall thickness / Vascular diameter (WT%). The expressions of MMP-9, TIMP and PCNA in pulmonary vascular smooth muscle cells were detected by immunohistochemistry. The correlation between the expression of PCNA and vascular remodeling was analyzed. Results (1) The degree of pulmonary vascular inflammation, WA% and WT% in chronic obstructive pulmonary disease group were significantly higher than those in control group (P <0.01). (2) The expression of PCNA, MMP-9 and TIMP-1 in pulmonary vascular smooth muscle cells was significantly higher than that in the control group (P <0.01). (3) Correlation analysis: The expression of MMP-9 and TIMP-1 in chronic obstructive pulmonary disease group was positively correlated with the degree of vascular inflammation, WA%, WT% and PCNA (P <0.01). Multiple linear regression analysis showed that MMP- The up-regulation of TIMP-1 expression was the main factor influencing pulmonary vascular remodeling (WA%, WT%) (P <0.01). Conclusion The enhanced expression of MMP-9 and TIMP-1 may cause the abnormal degradation of extracellular matrix, induce the proliferation of smooth muscle cells and promote the migration of inflammatory cells, which plays an important role in pulmonary vascular remodeling.