特发性肺纤维化患者蛋白C系统的研究

目的观察在特发性肺纤维化(IPF)患者支气管肺泡灌洗液(BALF)中凝血酶-抗凝血酶复合物(TAT)和Ⅲ型前胶原(PCⅢ)质量浓度的变化及二者间的相关性。观察IPF患者BALF和血浆中蛋白C(PC)、蛋白S(PS)及血栓调节蛋白(TM)水平的变化,探讨PC系统内各成分质量浓度的变化及其对肺内凝血活性的升高及肺纤维化形成的影响。方法选取正常对照16例,IPF患者16例。IPF患者及8例正常对照行支气管镜检查后取BALF并同时抽血留取血浆,其余8例对照仅留取血浆。采用ELISA法测定BALF及血浆TAT、PC、PS、TM质量浓度及BALF中PCⅢ质量浓度。结果IPF组BALF中PCⅢ和TM质量浓度明显高于对照组(P<0.01,P<0.05),PS质量浓度明显低于对照组(P<0.05)。IPF组血浆中TAT质量浓度明显高于对照组(P<0.01),PC质量浓度明显低于对照组(P<0.05)。IPF组BALF中PCⅢ质量浓度与TAT质量浓度呈线性正相关(r=0.52,P<0.05)。结论IPF患者存在血液的高凝状态。IPF患者肺内凝血活性的升高,与肺内胶原代谢的活动性及肺纤维化的形成相关。IPF患者存在PC及PS质量浓度的下降及TM质量浓度的升高,提示PC途径作用的减弱与凝血活性的升高及肺纤维化的形成具有一定的关系。

Protein C Anticoagulant System in Patients with Idiopathic Pulmonary Fibrosis

Objective To determine the change of clotting activation-thrombin-antithrombin Ⅲ complex(TAT) and collagen metabolism-procollagen Ⅲ(PCⅢ),and investigate the correlation between TAT and PCⅢ in bronchoalveolar lavage fluid(BALF) of patients with idiopathic pulmonary fibrosis(IPF).To determine the change of protein C(PC),protein S(PS),thrombomodulin(TM) and TAT levels in BALF and plasma of the patients with IPF,and to investigate the correlation between the change of Protein C anticoagulant system and the procoagulant activity as well as the pulmonary fibrosis.Methods 16 patients with IPF and 16 healthy individuals were inrolled and investigated.The bronchoalveolar lavage was performed to all patients with IPF and 8 healthy ones of control.Plasma was collected at the same time.The levels of TM,PC,PS,PCⅢ and TAT in the BALF and plasma also PCⅢ in BALF were measured using ELISA assays.Results The levels of PCⅢ and TM in BALF were significantly higher in patients with IPF than control subjects(P<0.01,P<0.05),the levels of PS in BALF were decreased as compared with the control subjects(P<0.05).The levels of TAT in plasma were significantly higher in patients with IPF than control subjects(P<0.01),the levels of PC were decreased as compared with the control subjects(P<0.05).The BALF concentration of PCⅢ was proportionally correlated with concentration of TAT in BALF(r=0.52,P<0.05).Conclusion Excessive procoagulant activity exists in patients with IPF.Excessive procoagulant activity in the alveolar space and lung interstitium may play a relevant role in the pathogenesis of IPF.Decreased PC,PS level and increased thrombomodulin level were observed in patient with IPF,and impairment of PC pathway was the reason for the excessive procoagulant activity of IPF and may promote lung fibrosis.