慢性阻塞性肺疾病急性加重期血浆LPA含量变化及肝素的影响

Changes of plasma lysophosphatidic acid levels in acute exacerbation of chronic obstructive pulmonary disease and the effects of LMWH

目的：观察慢性阻塞性肺疾病急性加重（ AECOPD）期患者血浆溶血磷脂酸（ LPA）含量变化及低分子肝素的影响。方法收集2010年5月至2013年6月住院的65例AECOPD患者及治疗后稳定期慢性阻塞性肺疾病（ SCOPD）患者纳入本研究。将65例AECOPD患者随机分为肝素治疗组和普通治疗组。测定治疗前后患者血浆LPA含量、血气及肺功能。60例年龄≥60岁的健康体检者作为对照组。血浆LPA含量测定采用层析技术结合改良的无机磷定量方法。结果65例AECOPD患者治疗前血浆LPA含量为（4.22±1.23）μmol/L，显著高于对照组[（2.55±0.49）μmol/L]（P〈0.01）及治疗后[（3.26±1.19）μmol/L]（P〈0.05）。AECOPD患者普通治疗后血浆LPA含量高于对照组（P〈0.05）。AECOPD患者治疗后血浆LPA水平均明显降低（P〈0.05，P〈0.01）；肝素添加治疗较普通治疗血浆LPA水平下降更明显（P〈0.05）。治疗后动脉二氧化碳分压（PCO2）、动脉氧分压（PO2）、1秒钟用力呼气容积占用力肺活量的比值（FEV1/ FVC）、1秒钟用力呼气容积（FEV1）等指标明显改善（P〈0.01）。肝素添加治疗较普通治疗能更明显改善上述指标（P〈0.05）。治疗前血浆LPA与 PCO2呈正相关（r＝0.61，P〈0.01），与PO2（r＝-0.76，P〈0.01）、FEV1/ FVC（r＝-0.79，P〈0.01）和 FEV1呈负相关（r＝-0.75，P〈0.01）；肝素治疗后血浆LPA与PCO2呈正相关（r＝0.58，P〈0.01），与PO2（r＝-0.82，P〈0.01）、FEV1/ FVC（r＝-0.83，P〈0.01）、FEV1呈负相关（r＝-0.77，P〈0.01）。结论 AECOPD患者血浆LPA含量显著升高，提示血液处于活化、高凝或血栓形成状态。肝素添加治疗能显著降低血浆LPA水平，改善肺功能。LPA可能成为AECO-PD诊断及药物疗效判断新的血浆生物标记物。

Objective To observe the changes of plasma lysophosphatidic acid（ LPA）levels in patients with acute exacerbation of chronic obstructive pulmonary disease（ AECOPD ）and the effects of low molecular weight heparin（ LMWH）. Methods A total of 65 patients with AECOPD,60 cases of healthy volunteers as control were enrolled into the study. The 65 patients with AECOPD were randomly divided into heparin treatment group and general treatment group. The plasma LPA levels were detected by measuring its inorganic phosphorus after separation by chromatograph. Meanwhile,the effects of LMWH on plasma LPA levels were observed. Results The plasma LPA levels significantly increased in patients with AECOPD,as compared with controls and stable COPD（P〈0. 05）. Administration of LMWH for two weeks significantly lowered the LPA levels of patients,as compared with general treatment（ P〈0. 05）,and the lung function parameter FEV1/ FVC,FEV1 significantly improved（P〈0. 01）. Plasma LPA levels were positively correlated with PCO2 ,and negatively correlated with PO2 ,FEV1/ FVC,and FEV1 before or after treatment. Conclusions Plasma LPA levels significantly elevated in patients with AECOPD,suggesting that platelet activation,hypercoagulability or thrombosis. Heparin treatment can significantly reduce the plasma levels of LPA and improve the lung function. LPA may be used as a new biomarker for patients with AECOPD.