中华结核和呼吸杂志
中華結覈和呼吸雜誌
중화결핵화호흡잡지
Chinese Journal of Tuberculosis and Respiratory Diseases
2008年
2期
129-133
,共5页
孔英君%孙文学%张一梅%石玉枝
孔英君%孫文學%張一梅%石玉枝
공영군%손문학%장일매%석옥지
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
肺疾病,慢性阻塞性%基質金屬蛋白酶類組織抑製劑%基質金屬蛋白酶%胞間黏附因子1
폐질병,만성조새성%기질금속단백매류조직억제제%기질금속단백매%포간점부인자1
Pulmonary disease,chronic obstructive%Tissue inhibitor of metalloproteinases%Matrix metalloproteinases%Intercellular adhesion molecule-1
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(MMP-9)、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、MMP-9、ICAM-1的蛋白和mRNA表达,并进行相关性分析.结果 MMP-9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MMP-9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MMP-9、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、MMP-9与ICAM-1的mRNA表达水平呈直线正相关,MMP-9与ICAM-1蛋白表达水平呈显著正相关.MMP-9和ICAM-1的mRNA及蛋白表达水平、TIMP-1的mRNA表达水平与FEV1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.
目的 研究COPD患者肺組織中基質金屬蛋白酶抑製劑-1(TIMP-1)、基質金屬蛋白酶-9(MMP-9)、細胞黏附因子-1(ICAM-1)蛋白和mRNA的分佈和錶達,探討其與氣流阻塞的關繫及吸煙對其影響.方法 取39例因肺癌行肺葉切除的癌徬肺組織標本,其中不吸煙不伴COPD組(A組)9例、吸煙不伴COPD組(B組)11例、吸煙伴COPD組(C組)19例.用免疫組化和逆轉錄聚閤酶鏈反應方法檢測TIMP-1、MMP-9、ICAM-1的蛋白和mRNA錶達,併進行相關性分析.結果 MMP-9錶達于肺泡上皮細胞、支氣管上皮細胞、血管平滑肌細胞、肺泡巨噬細胞、間質細胞,C組MMP-9免疫組化暘性細胞數(54.0±15.0)明顯高于A組和B組(1.2±0.7和1.4±0.8);TIMP-1蛋白錶達的主要部位為肺泡巨噬細胞、肺泡上皮細胞、毛細血管內皮細胞、血管平滑肌細胞,C組弱錶達,A組和B組無錶達;ICAM-1主要錶達于肺泡上皮細胞,C組ICAM-1免疫組化暘性細胞數(52.1±13.4)明顯高于A組和B組(2.1±1.1和4.5±2.4).C組MMP-9、TIMP-1、ICAM-1的mRNA平均吸光度值(0.71±0.16、0.47±0.10、0.62±0.15)明顯高于A組(0.17±0.05、0.20±0.06、0.37±0.11)和B組(0.20±0.08、0.26±0.08、0.44±0.12).C組肺組織TIMP-1、MMP-9與ICAM-1的mRNA錶達水平呈直線正相關,MMP-9與ICAM-1蛋白錶達水平呈顯著正相關.MMP-9和ICAM-1的mRNA及蛋白錶達水平、TIMP-1的mRNA錶達水平與FEV1佔預計值%、FEV1/FVC佔預計值%均呈顯著負相關.結論 TIMP-1、MMP-9和ICAM-1在促進炎性細胞遷移進入細胞外基底膜及氣道上皮細胞,導緻肺組織破壞和重塑,引起及加重COPD患者的氣流阻塞中起著重要作用.
목적 연구COPD환자폐조직중기질금속단백매억제제-1(TIMP-1)、기질금속단백매-9(MMP-9)、세포점부인자-1(ICAM-1)단백화mRNA적분포화표체,탐토기여기류조새적관계급흡연대기영향.방법 취39례인폐암행폐협절제적암방폐조직표본,기중불흡연불반COPD조(A조)9례、흡연불반COPD조(B조)11례、흡연반COPD조(C조)19례.용면역조화화역전록취합매련반응방법검측TIMP-1、MMP-9、ICAM-1적단백화mRNA표체,병진행상관성분석.결과 MMP-9표체우폐포상피세포、지기관상피세포、혈관평활기세포、폐포거서세포、간질세포,C조MMP-9면역조화양성세포수(54.0±15.0)명현고우A조화B조(1.2±0.7화1.4±0.8);TIMP-1단백표체적주요부위위폐포거서세포、폐포상피세포、모세혈관내피세포、혈관평활기세포,C조약표체,A조화B조무표체;ICAM-1주요표체우폐포상피세포,C조ICAM-1면역조화양성세포수(52.1±13.4)명현고우A조화B조(2.1±1.1화4.5±2.4).C조MMP-9、TIMP-1、ICAM-1적mRNA평균흡광도치(0.71±0.16、0.47±0.10、0.62±0.15)명현고우A조(0.17±0.05、0.20±0.06、0.37±0.11)화B조(0.20±0.08、0.26±0.08、0.44±0.12).C조폐조직TIMP-1、MMP-9여ICAM-1적mRNA표체수평정직선정상관,MMP-9여ICAM-1단백표체수평정현저정상관.MMP-9화ICAM-1적mRNA급단백표체수평、TIMP-1적mRNA표체수평여FEV1점예계치%、FEV1/FVC점예계치%균정현저부상관.결론 TIMP-1、MMP-9화ICAM-1재촉진염성세포천이진입세포외기저막급기도상피세포,도치폐조직파배화중소,인기급가중COPD환자적기류조새중기착중요작용.
Objective To evaluate the correlation between the expressions of intercellular adhesion molecule-1(ICAM-1)and tissue inhibitor of metalloproteinase-1(TlMP-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 difrerences 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 COPD group(52.1±13.4),(2.1±1.1)and(4.5±2.4).The mRNA level of MMP-9 showed significant difierence 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-1 and 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.
