慢性阻塞性肺疾病患者肺组织中基质金属蛋白酶抑制剂-1及基质金属蛋白酶-9与细胞黏附因子表达的关系被引量：19

Relationships between the expressions of intercellular adhesion molecule-1 and tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 in lung tissues of patients with chronic obstructive pulmonary disease

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摘要目的研究COPD患者肺组织中基质金属蛋白酶抑制剂-1（TIMP-1）、基质金属蛋白酶．9（MMPO）、细胞黏附因子-1（ICAM-1）蛋白和mRNA的分布和表达，探讨其与气流阻塞的关系及吸烟对其影响。方法取39例因肺癌行肺叶切除的癌旁肺组织标本，其中不吸烟不伴COPD组（A组）9例、吸烟不伴COPD组（B组）11例、吸烟伴COPD组（C组）19例。用免疫组化和逆转录聚合酶链反应方法检测TIMP．1、MMPO、ICAM-1的蛋白和mRNA表达，并进行相关性分析。结果MMPO表达于肺泡上皮细胞、支气管上皮细胞、血管平滑肌细胞、肺泡巨噬细胞、间质细胞，C组MMPO免疫组化阳性细胞数（54．0±15．0）明显高于A组和B组（1．2±0．7和1．4±0．8）；TIMP-1蛋白表达的主要部位为肺泡巨噬细胞、肺泡上皮细胞、毛细血管内皮细胞、血管平滑肌细胞，C组弱表达，A组和B组无表达；ICAM-1主要表达于肺泡上皮细胞，C组ICAM-1免疫组化阳性细胞数（52．1±13．4）明显高于A组和B组（2．1±1．1和4．5±2．4）。C组MMPO、TIMP-1、ICAM-1的mRNA平均吸光度值（0．71±0．16、0．47±0．10、0．62±0．15）明显高于A组（0．17±0．05、0．20±0．06、0．37±0．11）和B组（0．20±0．08、0．26±0．08、0．44±0．12）。C组肺组织TIMP-1、MMPO与ICAM-1的mRNA表达水平呈直线正相关，MMPO与ICAM-1蛋白表达水平呈显著正相关。MMPO和ICAM-1的mRNA及蛋白表达水平、TIMP-1的mRNA表达水平与FEV，占预计值％、FEV1／FVC占预计值％均呈显著负相关。结论TIMP-1、MMP-9和ICAM-1在促进炎性细胞迁移进入细胞外基底膜及气道上皮细胞，导致肺组织破坏和重塑，引起及加重COPD患者的气流阻塞中起着重要作用。 Objective To evaluate the correlation between the expressions of intercellular adhesion molecule-1 （ ICAM-1 ） and tissue inhibitor of metalloproteinase-1 （ TIMP-1 ） and matrix metalloproteinase-9 （MMP-9） in lung tissues of patients with COPD. Methods Lung tissues from patients with COPD （ COPD group, n = 19 ） and those without COPD （ smokers and nonsmokers with normal lung function, n -11 and 9, respectively） were obtained from surgical excisions of lung cancer patients. The mRNA expression of ICAM- 1, TIMP-1 and MMP-9 was detected using semi-quantitative RT-PCR. The protein expression of ICAM-1, TIMP-1 and MMP-9 was detected by using immunohistochemistry method. Results There were significant differences in FEV1% and FEV1/FVC% among smokers without COPD, nonsmokers without COPD and COPD patients. MMP-9 was highly expressed in alveolar epithelial cells, bronchial epithelial cells, vascular smooth muscle cells, alveolar macrophages, and interstitial cells in the COPD group, compared with smokers without COPD group and nonsmokers without COPD group （54.0 ± 15.0）, （ 1.2 ± 0. 7 ） and （ 1.4 ± 0. 8 ）.Low level expression of TIMP-1 was detected in alveolar macrophages, alveolar epithelial cells and vascular smooth muscle cells in the COPD group, but no expression in smokers and nonsmokers without COPD. High level expression of ICAM-1 was detected in alveolar epithelial cells, and the expression was higher in the COPDgroup （52.1 ± 13.4）, （2.1 ±1.1） and （4.5 ±2.4）. The mRNA level of MMP-9 showed significant difference among patients with COPD, smokers without COPD and nonsmokers without COPD （0.71 ±0. 16）, （0.20±0.08） and （0. 17±0.05）. The mRNA level of TIMP-1 was also significantly different among patients with COPD, smokers without COPD and nonsmokers without COPD （0. 47 ±0. 10）, （ 0. 26 ±0.08 ） and （0. 20± 0. 06）. ICAM expression was also significantly higher in patients with COPD as compared with smokers without COPD and nonsmokers without COPD （0. 62 ±0. 15）, （0. 44 ±0. 12） and （0. 37 ±0. 11 ）. Both the mRNA and the protein levels of MMP-9 were inversely correlated with FEV1% and FEV1/FVC% （r = -0. 759, -0. 756, -0. 772, -0. 725, respectively, P 〈0.01）. TIMP-1 mRNA level was inversely correlated with FEV1% and FEV1/FVC% （r = -0. 675, -0. 623, respectively P 〈0.01 ）. Negative correlations were also noted between ICAM-1 expressions （both mRNA and protein） and FEV1 % or FEV1/FVC% （r = - 0. 580, -0. 531, - 0. 739, - 0. 756, respectively P 〈 0.01 ）. Interestingly, the mRNA expression of TIMP-1, MMP-9 and ICAM-1 was positively correlated （ r = 0. 576, 0. 524, P 〈 0. 01 ）, while the protein levels of MMP-9 and ICAM-1 were positively correlated （ r = 0. 964, P 〈 0. 01 ）. Conclusion There was a significant correlation between over-expression of ICAM-1 and TIMP-land MMP-9 in lung tissues from COPD patients. Over-expressions of ICAM-1 in the lung may result in accumulation of inflammatory cells releasing certain inflammatory factors that could destroy the normal lung structure. In addition, highly expressed TIMP-1 and MMP-9 in lung tissues may also contribute to the destruction and reconstitution of the bronchial or/and alveolar wall, which is likely to play a major role in airway obstruction.

作者孔英君孙文学张一梅石玉枝

机构地区哈尔滨医科大学附属第一医院呼吸内科

出处《中华结核和呼吸杂志》 CAS CSCD 北大核心 2008年第2期129-133,共5页 Chinese Journal of Tuberculosis and Respiratory Diseases

基金黑龙江省自然科学基金资助项目（D200655）

关键词肺疾病慢性阻塞性基质金属蛋白酶类组织抑制剂基质金属蛋白酶胞间黏附因子1 Pulmonary disease, chronic obstructive Tissue inhibitor of metalloproteinases Matrix metalloproteinases Intercellular adhesion molecule-1

分类号 R686 [医药卫生—骨科学]

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