IL-5、IL-12、MMP-9和TIMP-1在不同海拔地区慢性阻塞性肺疾病合并慢性肺源性心脏病患者血清中的表达及意义

Variations of IL-5, IL-12, MMP-9 and TIMP-1 in patients with chronic obstructive pulmonary disease accompanied by chronic pulmonary heart disease residing at different altitudes

目的 通过检测中、高海拔地区慢性阻塞性肺疾病（COPD）合 并 慢 性 肺 源 性 心 脏 病（CPHD）患者血清白介素5（IL-5）、IL-12、基质金属蛋白酶9（MMP-9）和金属蛋白酶组织抑制剂1（TIMP-1）的变化水平并探讨其临床意义。方法 选取 2012年 9月至 2014年 8月青海省西宁市 （中度海拔,2260m）COPD合并 CPHD患者和健康体检者各30例、青海省玉树州 （高海拔,3680m）相同疾病患者 22例和健康体检者24例,采用 酶联免疫吸附试验法分别测定其血清IL-5、IL-12、MMP-9及 TIMP-1的表达水平并进行比较。结果 中、高海拔病例组血清IL-5水平均低于其对照组（t=4.069、4.530,P 值均〈0.01）,高海拔病例组和对照组的血清IL-5水平均高于中海拔病例组和对照组 （t=14.118、20.284,P 值均〈0.01）;中、高海拔病例组血清IL-12水平均高于其对照组 （t=5.967、2.274,P 值均〈0.05）,高海拔病例组血清IL-12水平低于中海拔病例组 （t=2.598,P 〈0.05）;中、高海拔病例组血清 MMP-9水 平 均 高 于 其 对 照 组 （t=21.032、10.308,P 值 均 〈0.01）,高海拔病例组和对照组的血清 MMP-9水平高于中海拔的病例组和对照组 （t=6.991、10.771,P 值均〈0.01）;中海拔病例组血清 TIMP-1水平高于其对照组 （t=6.626,P 〈0.01）,中海拔病例组和对照组血清 TIMP-1水平均高于高海拔病例组和对照组 （t=7.015、3.292,P 值均 〈0.01）,高海拔病例组和对照组的血清 TIMP-1水平差异无统计学意义 （t=0.228,P〉0.05）。结论 中、高海拔地区 COPD合并 CPHD患者血清中IL-5、IL-12、MMP-9及 TIMP-1表达水平发生了相应的变化,其水平变化可能参与了气道免疫炎症反应和气道重塑;同时,上述炎症因子在不同海拔地区之间表达具有一定差异,考虑高原缺氧环境更易诱发和加重机体炎症反应。

Objective To investigate the changes and implications of interleukin-5 （IL-5）, IL-12, matrix metalloproteinase-9 （MMP-9） and tissue inhibitor of metalloproteinase-1 （TIMP-1） in patients with chronic obstructive pulmonary disease （COPD） accompanied by chronic pulmonary heart disease （CPHD）. Methods A total of 30 patients with COPD associated with CPHD as well as 30 healthy controls, residing at a medium altitude of 2 260 m, were recruited in the present study. In addition, 22 patients with COPD associated with CPHD as well as 24 healthy controls, residing at a high altitude of 3 680 m were included in the study. The serum levels of IL-5, IL-12, MMP-9 and TIMP-1 were measured using enzyme-linked immunosorbent assay. Results The serum levels of IL-5 of patients in the medium and high-altitude groups were lower than those of their corresponding controls （ t = 4. 069,4. 530, both P %0.01）. The IL-5 levels in the high-altitude group and its controls were higher than those in the medium- altitude group and its controls （ t = 14. 118,20. 284, both P〉0.01）. The serum levels of IL-12 in the medium and high-altitude groups were higher than those of their corresponding controls （ t = 5. 967, 2. 274, both P 〈0.05）. The IL-12 levels in the high-altitude patients were lower than those in the medium-altitude patients （ t =2. 598, P d0.05）. The serum levels of MMP-9 in the medium and highaltitude groups were higher than those of their corresponding controls （ t = 21. 032, 10. 308, both P〉0.01）. The MMP-9 levels in the high-altitude group and its controls were higher than those in the medium-altitude group and its controls （ t =6. 991,10.771,both P 〈0.01）. The serum levels of TIMP-1 in the medium-altitude patients were higher than those of its controls （ t = 6. 626, P 〈0.01）. The TIMP- 1 levels of patients in the medium altitude group and its control group were higher than those in the high- altitude group and its controls （ t = 7. 015, 3. 292, both P 〈 0.01）. No significant differences were observed in the serum levels of TIMP-1 between the high-altitude group and its controls （ t =0. 228, P 〉 0.05）. Conclusions The serum levels of IL-5, IL-12, MMP-9 and T1MP-1 were changed in patients with COPD accompanied by CPHD at medium and high-altitude regions, these alterations may be involved in airway inflammatory response and airway remodeling. We found some different expressions of inflammatory eytokine in different altitudes, and the reason was that high altitude anoxia exaggerated systemic inflammatory response of COPD.