Fractalkine与慢性阻塞性肺疾病并肺源性心脏病患者氧化应激相关性及机制探讨

目的探讨Fractalkine(FKN)与慢性阻塞性肺疾病(COPD)并肺源性心脏病(简称肺心病)患者氧化应激状态的相关性及可能机制。方法 64例AECOPD住院患者按是否合并肺心病、是否使用乙酰半胱氨酸(NAC)、COPD严重程度以及心功能分为8组,8例志愿者为正常对照组,测定各组患者住院次日、治疗后第10天血清各项指标,并检查心脏彩超、肺功能、CAT评分。结果血清FKN、NF-κB、OX-LDL及hs CRP水平在AECOPD的各组患者中均较正常对照组升高(P0.05),重症组及失代偿组升高明显(P0.05),肺心病组治疗前及治疗后均高于COPD组(P0.05),在COPD轻症干预组及肺心病代偿干预组治疗后下降明显(P0.05),SOD则相反。FEV1在肺心病代偿干预组及COPD轻症干预组治疗后较治疗前升高(P0.05)。肺动脉压在肺心病代偿干预组治疗前后有显著差异(P0.05),肺心病失代偿组较代偿组明显升高(P0.05),肺心病组与COPD组比较有显著差异(P0.05)。CAT评分除在肺心病失代偿组外其它各组治疗前后均有显著差异(P0.05),肺心病组与COPD组比较有统计学差异(P0.05)。治疗前8组患者血清FKN与CAT评分及NF-κB、OX-LDL、hs CRP、肺动脉压呈正相关(r=0.417,0.521,0.401,0.456,0.395,P0.05),与SOD负相关(r=-0.387,P0.05),与FEV1无明显相关性(r=0.215,P0.05)。结论 COPD并肺源性心脏病存在的氧化应激,与FKN密切相关,其机制可能系COPD持续低氧引起的氧化应激产物增多,激活NF-κB而促进FKN的生成和释放,NAC可能通过NF-κB途径降低FKN的生成,对早期肺心病的预防有一定作用。

Investigate the mechanism and the relationship between fractalkine and oxidative stress of patients with COPD and pulmonary heart disease

Objective To investigate the mechanism and the relationship between fractalkine and oxidative stress of patients with COPD and pulmonary heart disease.Methods 64 patients with AECOPD were divided into the following 8 groups according to whether merger pulmonary heart disease,whether using NAC,Cardiac function and GOLD classification of COPD disease severity.8 healthy volunteers were selected as control group.Blood samples before and 10 days after treatment were collected to detect the level of all serum indicators,Color Doppler echocardiography,lung function and CAT score were also examined.Results Levels of FKN,NF-κB,OX-LDL and hsCRP in different groups of AECOPD patients were higher than healthy control (P＜0.05) and all of them were higher in severe group than mild group (P＜0.05).Also,before and after treatment,those in pulmonary heart disease group were higher than COPD group,but decreased significantly in COPD+NAC group and mild cases of pulmonary heart disease + NAC group (P＜0.05).SOD,on the contrary.Administration of NAC resulted in elevated FEV1 in mild cases of COPD group and pulmonary heart disease group (P＜0.05).Pulmonary arterial pressure changed strikingly in the mild cases of pulmonary heart disease + NAC group after treatment (P＜0.05),Compared to mild cases of pulmonary heart disease patients,higher pulmonary arterial pressure existed in severe cases.Compared with COPD group,the pulmonary artery pressure of pulmonary heart disease group was significantly higher (P＜0.05).Besides,in severe cases of pulmonary heart disease group,CAT score in other groups altered significantly before and after treatment (P＜0.05).Also,marked difference was seen between COPD group and pulmonary heart disease group(P＜0.05);The level of FKN was positively correlated with CAT score,NF-κB,OX-LDL,hsCRP and pulmonary artery pressure (r =0.417,0.521,0.401,0.456,0.395,P＜0.05),and negatively correlated with SOD(r=-0.387,P＜0.05),while had no obvious correlation with FEV1 (r =0.215,P＞0.05).Conclusions Oxidative stress in patients with COPD and cor pulmonale is closely related to FKN,Hypoxemia causes an increase in ROS,which activates the NF-κB and promotes FKN to generate and release.NAC could inhibit ROS generation,which prevents the activation of NF-κB and reduces the production of FKN.Our results show that NAC may be helpful for prevention of COPD and pulmonary heart disease in early stage.