稳定期COPD患者血清suPAR、IL-8、MMP-9的水平及其意义
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摘要
目的分析稳定期慢性阻塞性肺疾病患者血浆可溶性尿激酶型纤溶酶原激活因子受体(suPAR)、IL-8和MMP-9的水平,探讨其在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者中的临床意义。方法入选60例稳定期COPD患者设为观察组,再根据肺功能分为Ⅱ级、Ⅲ级及Ⅳ级亚组;同时选取同期健康体检者70例作为对照组,检测两组的血清suPAR、IL-8和MMP-9水平及肺功能,比较观察组跟对照之间的差异,同时比较Ⅱ级、Ⅲ级、Ⅳ级亚组及对照组之间的差异。结果观察组血清suPAR、IL-8和MMP-9水平高于对照组;Ⅱ级、Ⅲ级及Ⅳ级各亚组的血清suPAR、IL-8和MMP-9均高于对照组;Ⅲ级及Ⅳ级组高于Ⅱ级组;以上差异均有统计学意义(P<0.05)。但Ⅲ级与Ⅳ级比较无差异(P>0.05)。结论血清suPAR、IL-8和MMP-9在稳定期COPD患者中水平增高,且反映了其严重程度,有望成为COPD病情评估新指标及未来分子水平治疗的新靶点。
Objective To analyze the serum soluble urokinase-type plasminogen activator receptor,IL-8 and MMP-9 levels in stable chronic obstructive pulmonary disease and explore its clinical significance. Methods 60 patitents with stable COPD were selected as the observation group,and subdivided to subgroups stage Ⅱ,Ⅲ and Ⅳ. Meanwhile,70 healthy individuals were enrolled as the control group. And then suPAR、IL-8 and MMP-9 levels and pulmonary function were measured in both groups. The differences between both groups as well as all the subgroups were compared. Results The suPAR level of the observation group was higher than that of the control group. Also,compared with the control group,stage Ⅱ,Ⅲand Ⅳ subgroups showed much higher level of suPAR,IL-8,MMP-9. And it was higher in stageⅢand Ⅳthan in stageⅡ.However,there was no difference between Stage Ⅲ and Ⅳ. Conclusion The suPAR,IL-8 and MMP-9 level are higher in COPD patients and are related to the severity of stages. Therefore,it could be an appropriate biomarker as well as a novel target for future therapy and further evaluation.
Objective To analyze the serum soluble urokinase-type plasminogen activator receptor,IL-8 and MMP-9 levels in stable chronic obstructive pulmonary disease and explore its clinical significance. Methods 60 patitents with stable COPD were selected as the observation group,and subdivided to subgroups stage Ⅱ,Ⅲ and Ⅳ. Meanwhile,70 healthy individuals were enrolled as the control group. And then suPAR、IL-8 and MMP-9 levels and pulmonary function were measured in both groups. The differences between both groups as well as all the subgroups were compared. Results The suPAR level of the observation group was higher than that of the control group. Also,compared with the control group,stage Ⅱ,Ⅲand Ⅳ subgroups showed much higher level of suPAR,IL-8,MMP-9. And it was higher in stageⅢand Ⅳthan in stageⅡ.However,there was no difference between Stage Ⅲ and Ⅳ. Conclusion The suPAR,IL-8 and MMP-9 level are higher in COPD patients and are related to the severity of stages. Therefore,it could be an appropriate biomarker as well as a novel target for future therapy and further evaluation.
引文
[1]VOGELMEIER C F,CRINER G J,MARTINEZ J,et al.Global strategy for the diagnosis,management,and prevention of chronic obstructive pulmonary disease 2017 report[EB/OL].(2016-11-16)[2016-12-09].http://goldcopd.org/
[2]中华医学会呼吸病学分会,慢性阻塞性肺疾病诊治指南[J].中华结核和呼吸杂志,2013,36(4):255-264.
[3]SIN D D,MAN S F.Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases?The potential role of systemic inflammation in chronic obstructive pulmonary disease[J].Circulation,2003,107(11):1514-1519.
[4]de TORRES J P,PINTO-PLATA V,CASANOVA C,et al.C-reactive protein levels and survival in patients with moderate to very severe COPD[J].Chest,2008,133(6):1336-1343.
[5]OWEN C A.Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2008,3(2):253-268.
[6]RAGNO P.The urokinase receptor:a ligand or areceptor?Story of a sociable molecule[J].Cell Mol Life,2006,63(9):1028-1037.
[7]TUNC T,CEKMEZ F,YILDIRIM S,et al.Predictive value of soluble urokinase plasminogen activator receptor,soluble ST2,and IL-33 in bronchopulmonary dysplasia[J].Pediatr Res,2014,75(6):788-792.
[8]PORTELLI M A,SIEDLINSKI M,STEWART C E,et al.Genome mapping identifies human plasma kallikrein as a post translational regulator of serum u PAR levels[J].FASEB J,2014,28(2):923-934.
[9]SHINKAI M,GREGORY H F,BRUCE K R.Macrolide antibiotics modulate ERK phosphorulation and IL-8 and GM-CSF production by human bronchial epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2006,290(1):75-85.
[10]于寰,张朝阳,范丽,等.COPD小气道重塑的HRCT研究及与肺功能的相关性[J].临床放射学杂志,2013,32(7):943-946.
[11]MEUNIER I,EMBURY-HYATT C,STEBNER S,et al.Virulence differences of closely related pandemic 2009H1N1 isolates correlate with increased inflammatory reponses in ferrets[J].Virology,2011,410(3):667-669.
[12]BEAUFORT N,LEDUC D,EGUCHI H,et al.The human airway trypsin-like protease modulates the urokinase receptor(u PAR,CD87)structure and functions[J].Am J Physiol Lung Cell Mol Physiol,2007,292(5):1263-1272.
[13]MONTUORI N,SELLERI C,RAGNO P.The urokinasereceptor in infectious diseases[J].Infez Med,2012,20:13-18.
[14]BARNES P J.The cytokine network in asthma and chronic obstructive pulmonary disease[J].J Clin Invest,2008,118(11):3546-3556.
[15]DONNELLY L E,BARNES P J.Chemokine receptors as therapeutic targets in Chronic obstructive disease[J].Trends Pharmacol Sci,2006,27:546-553.
[16]RIISBRO R,CHRISTENSEN I J,HOGDALL C,et al.Solubleurokinase plasminogen activator receptor measurements:influence of sample handling[J].Int J Biol Markers,2001,16(4):233-239.
[17]ANDERSEN O,EUGEN-OLSEN J,KOFOED K,et al.Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy[J].J Med Virol,2008,80(2):209-216.
[18]刘揆亮,吴静.尿激酶型纤溶酶原激活物受体及可溶性尿激酶型纤溶酶原激活物受体与炎症相关的研究进展[J].临床与病理杂志,2014,34(4):425-430.
[19]WANG Q,WANG Y,ZHANG Y,et al.The role of u PAR in epithelial-mesenchymal transition in small airway epithelium of patients with chronic obstructive pulmonary disease[J].Respir Res,2013,14(1):67.
[20]中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2013年修订版)[J].中国医学前沿杂志(电子版),2014,(6)2:67-80.
[2]中华医学会呼吸病学分会,慢性阻塞性肺疾病诊治指南[J].中华结核和呼吸杂志,2013,36(4):255-264.
[3]SIN D D,MAN S F.Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases?The potential role of systemic inflammation in chronic obstructive pulmonary disease[J].Circulation,2003,107(11):1514-1519.
[4]de TORRES J P,PINTO-PLATA V,CASANOVA C,et al.C-reactive protein levels and survival in patients with moderate to very severe COPD[J].Chest,2008,133(6):1336-1343.
[5]OWEN C A.Roles for proteinases in the pathogenesis of chronic obstructive pulmonary disease[J].Int J Chron Obstruct Pulmon Dis,2008,3(2):253-268.
[6]RAGNO P.The urokinase receptor:a ligand or areceptor?Story of a sociable molecule[J].Cell Mol Life,2006,63(9):1028-1037.
[7]TUNC T,CEKMEZ F,YILDIRIM S,et al.Predictive value of soluble urokinase plasminogen activator receptor,soluble ST2,and IL-33 in bronchopulmonary dysplasia[J].Pediatr Res,2014,75(6):788-792.
[8]PORTELLI M A,SIEDLINSKI M,STEWART C E,et al.Genome mapping identifies human plasma kallikrein as a post translational regulator of serum u PAR levels[J].FASEB J,2014,28(2):923-934.
[9]SHINKAI M,GREGORY H F,BRUCE K R.Macrolide antibiotics modulate ERK phosphorulation and IL-8 and GM-CSF production by human bronchial epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2006,290(1):75-85.
[10]于寰,张朝阳,范丽,等.COPD小气道重塑的HRCT研究及与肺功能的相关性[J].临床放射学杂志,2013,32(7):943-946.
[11]MEUNIER I,EMBURY-HYATT C,STEBNER S,et al.Virulence differences of closely related pandemic 2009H1N1 isolates correlate with increased inflammatory reponses in ferrets[J].Virology,2011,410(3):667-669.
[12]BEAUFORT N,LEDUC D,EGUCHI H,et al.The human airway trypsin-like protease modulates the urokinase receptor(u PAR,CD87)structure and functions[J].Am J Physiol Lung Cell Mol Physiol,2007,292(5):1263-1272.
[13]MONTUORI N,SELLERI C,RAGNO P.The urokinasereceptor in infectious diseases[J].Infez Med,2012,20:13-18.
[14]BARNES P J.The cytokine network in asthma and chronic obstructive pulmonary disease[J].J Clin Invest,2008,118(11):3546-3556.
[15]DONNELLY L E,BARNES P J.Chemokine receptors as therapeutic targets in Chronic obstructive disease[J].Trends Pharmacol Sci,2006,27:546-553.
[16]RIISBRO R,CHRISTENSEN I J,HOGDALL C,et al.Solubleurokinase plasminogen activator receptor measurements:influence of sample handling[J].Int J Biol Markers,2001,16(4):233-239.
[17]ANDERSEN O,EUGEN-OLSEN J,KOFOED K,et al.Soluble urokinase plasminogen activator receptor is a marker of dysmetabolism in HIV-infected patients receiving highly active antiretroviral therapy[J].J Med Virol,2008,80(2):209-216.
[18]刘揆亮,吴静.尿激酶型纤溶酶原激活物受体及可溶性尿激酶型纤溶酶原激活物受体与炎症相关的研究进展[J].临床与病理杂志,2014,34(4):425-430.
[19]WANG Q,WANG Y,ZHANG Y,et al.The role of u PAR in epithelial-mesenchymal transition in small airway epithelium of patients with chronic obstructive pulmonary disease[J].Respir Res,2013,14(1):67.
[20]中华医学会呼吸病学分会慢性阻塞性肺疾病学组.慢性阻塞性肺疾病诊治指南(2013年修订版)[J].中国医学前沿杂志(电子版),2014,(6)2:67-80.