慢性阻塞性肺疾病患者肺功能与基质金属蛋白酶9和淋巴细胞相关抗原1的关系

Association of pulmonary function with matrix metalloproteinase-9 and lymphocyte function-associated antigen-1 in patients with chronic obstructive pulmonary disease

目的:探讨慢性阻塞性肺疾病患者基质金属蛋白酶9和黏附分子配体淋巴细胞相关抗原1的表达以及二者与肺功能的关系。方法:选择2003-01/12河北省承德医学院附属医院呼吸科住院治疗的慢性阻塞性肺疾病患者35例。正常对照组为同期本院健康体检者25人。应用酶联免疫吸附法测定血清中基质金属蛋白酶9的含量;采用流式细胞术,用单克隆抗体定量测定周围血中粒细胞、淋巴细胞、单核细胞表面的淋巴细胞相关抗原1的表达率;应用肺功能测定系统(SensorMedicsS-2200型,美国)进行肺功能测定。检测结果与对照组比较并进行变量间相关性分析,其中慢性阻塞性肺疾病患者分别在入院第2天(加重期)及患者出院后病情稳定2个月(稳定期)进行2次上述指标的检测。结果:按意向处理分析,慢性阻塞性肺疾病组35例及正常对照组25人均进入结果分析。①血清基质金属蛋白酶9的含量:慢性阻塞性肺疾病组加重期和稳定期均高于对照组[(0.49±0.28,0.35±0.29,0.25±0.13)μg/L,(t=3.98,-1.60,P<0.05)];稳定期低于加重期(t=2.05,P<0.05)。②两组患者白细胞表面淋巴细胞相关抗原1的阳性表达率:急性加重期与稳定期粒细胞、单核细胞表面淋巴细胞相关抗原1的阳性表达率均高于正常对照组(P<0.05或0.01);稳定期粒细胞、单核细胞表面淋巴细胞相关抗原1阳性表达率较急性期明显下降[(89.43±4.03)%比(95.26±2.30)%,(92.7±2.04)%比(98.50±1.30)%,(t=7.43,14.18,P<0.01)]。③变量间相关性分析:慢性阻塞性肺疾病患者急性加重期淋巴细胞相关抗原1和基质金属蛋白酶9阳性表达率与第1秒用力肺活量占预计值的百分比呈负相关(r=-0.718,-0.689,P<0.05),基质金属蛋白酶9与残气量/肺总量的百分比呈正相关(r=0.710,P<0.05)。结论:慢性阻塞性肺疾病患者基质金属蛋白酶9的含量和急性加重期粒细胞及单核细胞表面淋巴细胞相关抗原1的表达分别与第1秒用力肺活量占预计值的百分比呈负相关,基质金属蛋白酶9与残气量/肺总量的百分比呈正相关。检测上述指标可以间接反映肺内炎症反应、气流受限及肺气肿的严重程度,以判断病情及预后。

AIM: To investigate the expressions of matrix metalloproteinases-9 and adhesion molecular ligand lymphocyte function-associated antigen-1(LFA-1) in patients with chronic obstructive pulmonary disease, and discuss their correlation with the pulmonary function. METHODS: Thirty-five patients with chronic obstructive pulmonary disease, who were hospitalized in the Department of Respiratory Medicine, the Affiliated Hospital of Chengde Medical College between January and December 2003, and 35 healthy physical examinees (normal control group) in this hospital at the same period, were involved in this study. The serum level of matrix metalloproteinases-9 was determined with enzyme-linked immunoadsorbent assay (ELISA); The expressive rates of lymphocyte function-associated antigen-1 on the surfaces of granulocyte, lymphocyte and monocyte in peripheral blood were quantitatively analyzed with monoclonal antibodies by using the technique of flow cytometry.The pulmonary function was determined with the pulmonary function measuring system (Sensor Medics S-2200 type, America). The results were compared with those in the control group, and the correlations among the variables were analyzed. The above indexes of the patients with chronic obstructive pulmonary disease group were examined again on the 2nd day after admission (the exacerbated phase) and 2 months after discharge (remission phase). RESULTS: According to intention-to-treat analysis, all the 35 patients in the chronic obstructive pulmonary disease group and 25 cases in the normal control group were involved in the analysis of results. ① Content of matrix metalloproteinases-9:It was higher in the chronic obstructive pulmonary disease group at both the exacerbated and remission phases than in the control group [(0.49±0.28), (0.35±0.29), (0.25±0.13) μg/L, t=3.98, -1.60, P < 0.05]; It was lower at the stationary phase than at the exacerbated phase (t=2.05, P < 0.05). ② The positive expressive rate of lymphocyte function-associated antigen-1 on the surface of leucocyte in the two groups: The positive expressive rates of lymphocyte function-associated antigen-1 on the surfaces of granulocytes and monocytes at the exacerbated and remission phases were higher than those in the normal control group (P < 0.05 or P < 0.01); Those were obviously decreased at the stationary phase than at the exacerbated phase [(89.43±4.03)% vs (95.26±2.30)%, (92.7±2.04)% vs (98.50±1.30)%, t=7.43, 14.18, P < 0.01]. ③ Correlation analysis among the variables: In the patients with chronic obstructive pulmonary diseases,the positive expressive rate of lymphocyte function-associated antigen-1 at the exacerbated phase and content of matrix metalloproteinases-9 had negative correlation with the percentage of the forced vital capacity in the first second to the predicted value (r =-0.718, -0.689, P < 0.05), matrix metalloproteinases-9 was positively correlated with the percentage of residual volume to total lung capacity (r = 0.710,P < 0.05). CONCLUSION: In patients with chronic obstructive pulmonary diseases, content of matrix metalloproteinases-9 and the expressive rate of lymphocyte function-associated antigen-1 on the surfaces of granulocytes and monocytes at the exacerbated phase has negative correlation with the percentage of the forced vital capacity in the first second to the predicted value respectively, matrix metalloproteinases-9 is positively correlated with the percentage of residual volume to total lung capacity. The detection of the above indexes can indirectly reflect the inflammatory reaction and restriction of air flow in lung and the severity of pulmonary emphysema, so as to judge the disease condition and prognosis.