血府逐瘀胶囊改善慢性阻塞性肺疾病高龄患者血栓前状态、炎症因子和呼吸功能及其相关性分析

Clinical efficacy and correlation analysis in elderly patients of chronic obstructive pulmonary disease with Xuefu Zhuyu Capsule

目的观察血府逐瘀胶囊辅助治疗对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)高龄患者血栓前状态、炎症因子和呼吸功能的影响。方法选取COPD急性加重期(AECOPD)、稳定期(COPD)血瘀证高龄患者各60例,按照数字表法随机化分组,稳定期分为COPD稳定期对照组(COPD1)和治疗组(COPD2);急性加重期分为急性加重期对照组(AECOPD1)和治疗组(AECOPD2)。COPD1和AECOPD1给予常规治疗,COPD2和AECOPD2在对照组基础上口服血府逐瘀胶囊治疗,疗程12周。各组治疗前后分别测定凝血酶原时间(prothrombin time,PT)、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)、凝血酶时间(thrombintime,TT),以及D-二聚体(D-dimer,DD)、凝血酶-抗凝血酶复合物(thrombin-antithrombin complex,TAT)、纤维蛋白原(fibrinogen,FIB)、血浆凝血酶原片段1+2(prothrombin fragment 1+2,F1+2)、血浆血管性假血友病因子(von Willebrand factor,v WF)、血管性血友病因子裂解酶(a disintegrin-like and metalloprotease with thrombospondin type I repeats-13,ADAMTS-13)、C-反应蛋白(C-reactive protein,CRP)、白细胞介素(interleukin,IL)-6、IL-8水平和动脉血气分析与肺功能。结果COPD和AECOPD患者,各自在性别、年龄、病程、体质量指数(body mass index,BMI)和上述检测指标基线比较,差异不显著,具有可比性。各组治疗前后比较,COPD1组PT明显缩短,IL-6、IL-8水平和动脉二氧化碳分压[p(CO_(2))]明显降低(P<0.05),CRP水平显著降低(P<0.01);COPD2组TT、PT显著缩短(P<0.05、0.01),DD、TAT、FIB、F1+2、v WF、CRP、IL-6、IL-8水平和动脉血氧分压[p(O_(2))]、p(CO_(2))显著降低,而ADAMST-13显著升高(P<0.01);AECOPD1组DD、TAT水平明显降低(P<0.05),APTT显著缩短,FIB、F1+2水平和炎症指标显著降低,ADAMST-13水平和p(O_(2))显著升高(P<0.01);AECOPD2组APTT、PT显著缩短(P<0.05、0.01),DD、TAT、FIB、F1+2、v WF和CRP、IL-6、IL-8水平和p(CO_(2))显著下降、ADAMST-13水平和p(O_(2))显著升高(P<0.01)。肺功能指标除COPD1组第一秒用力呼气量占用力肺活量的百分率(first second forced expiratory volume accounts for the percentage of FVC,FEV1%)外,各组治疗前后均有显著性差异(P<0.01)。治疗后,与COPD1组比较,COPD2组PT显著缩短,DD、TAT、F1+2、v WF、CRP水平和p(CO_(2))显著降低(P<0.01),IL-6水平明显降低(P<0.05),ADAMST-13水平和肺功能指标显著升高(P<0.01);与AECOPD1组比较,AECOPD2组PT、APTT显著缩短,DD、F1+2、v WF、CRP、IL-6水平和p(CO_(2))显著降低(P<0.01),TAT水平明显降低(P<0.05),ADAMST-13水平和FEV1%显著升高(P<0.01)。凝血功能与炎症指标和呼吸功能相关性分析结果提示,DD、FIB、F1+2、v WF、ADAMST-13高度相关;DD、FIB、F1+2、v WF与CRP、IL-6、IL-8、p(CO_(2))呈正相关,与Pa O_(2)、FEV1%、FEV1、FEV1/FVC呈负相关;ADAMST-13则相反。结论COPD稳定期和急性加重期均存在凝血纤溶系统失衡和内皮功能失调的血栓前状态。血府逐瘀胶囊联合治疗能够明显调节COPD高龄患者的高凝状态、改善炎症指标及肺功能,在急性加重期改善更明显,其可能的作用机制与其抑制血小板聚集、降低DD、抗纤维蛋白原水平和调节血管内皮功能有关。

Objective To observe the effects of Xuefu Zhuyu Capsule(血府逐瘀胶囊)on the pre-thrombotic state,inflammatory factors and respiratory function in elderly patients with chronic obstructive pulmonary disease(COPD).Methods They were selected and randomly divided,that sixty elderly patients with blood stasis syndrome in acute exacerbation stage(AECOPD group)and stable stage(COPD group).The control group was given routine treatment,and the treatment group was given Xuefu Zhuyu Capsule to promote blood circulation and remove blood stasis for a course of 12 weeks.Each group posttreatment was determined prothrombin time(PT),activated partial thromboplastin time(APTT),thrombin time(TT),D-dimer(DD),thrombin-antithrombin complex(TAT),fibrinogen(FIB),prothrombin fragment 1+2(F1+2),von Willebrand factor(v WF),a disintegrin-like and metalloprotease with thrombospondin type I repeats-13(ADAMTS-13),C-reactive protein(CRP),interleukin(IL)-6,IL-8 and arterial blood gas and lung function.Results Under the treatments,only PT,IL-6,IL-8,CRP and arterial partial pressure of carbon dioxide[p(CO_(2))]in COPD1 group had significant differences(P<0.05).They were significantly different(P<0.01)that PT,DD,TAT,FIB,F1+2,v WF and ADAMST-13,CRP,IL-6,IL-8,arterial partial pressure of oxygen[p(O_(2))]and p(CO_(2))in COPD2 group,and TT(P<0.05).There were significant differences in APTT,FIB,F1+2,ADAMST-13 and inflammatory indexes in AECOPD1 group(P<0.01),and DD and TAT(P<0.05).In the levels of PT,DD,TAT,FIB,endothelin and inflammation in AECOPD2 group(P<0.01),APTT and F1+2,VWF and ADAMST-13(P<0.01).Lung function was significant differences among all groups,except for first second forced expiratory volume accounts for the percentage of FVC(FEV1%)in COPD1 group.After treatment,compared with COPD1 group,PT in COPD2 group was significantly shortened,the levels of DD,TAT,F1+2,v WF,CRP and p(CO_(2))were significantly decreased(P<0.01),the level of IL-6 was significantly decreased(P<0.05),and the level of ADAMST-13 and lung function indexes were significantly increased(P<0.01);compared with AECOPD1 group,PT and APTT in AECOPD2 group were significantly shortened,the levels of DD,F1+2,VWF,CRP,IL-6 and p(CO_(2))were significantly decreased(P<0.01),and the level of TAT was significantly decreased(P<0.05),the levels of ADAMST-13 and FEV1%were significantly increased(P<0.01).The results of correlation analysis showed that DD and FIB were highly correlated with F1+2,VWF and ADAMST-13.DD,FIB,F1+2,and VWF were positively correlated with CRP,IL-6,IL-8,p(CO_(2)),and negatively with p(O_(2)),FEV1,FEV1,FEV1/FVC.ADAMST-13 did the opposite.Conclusion The patients with COPD had a prethrombotic state with imbalance of coagulation and fibrinolysis system and dysfunction of endothelium.Xuefu Zhuyu Capsule can obviously adjust the hypercoagulability,improve inflammation and lung function.The possible mechanism of action is related to inhibition of platelet aggregation,reduction of DD,antifibrinogen and regulation of vascular endothelial function.