慢性阻塞性肺疾病与凝血-纤溶功能异常

慢性阻塞性肺疾病（COPD）是以气道、肺实质和肺血管的慢性炎症为特征。因肺内通气血流比例失调致慢性缺氧，可继发红细胞增多和血黏滞度增高，引起血流高黏、高聚、高凝及微血栓形成。COPD急性加重期凝血-纤溶功能异常进一步恶化，对病情进展的影响已经为临床高度关注。研究同时发现COPD与静脉血栓栓塞症（VTE）关系密切，其合并深静脉血栓（DVT）甚至肺血栓栓塞症（PTE）已成为重要的医疗保健问题。     

滇白珠水提物对慢性阻塞性肺疾病大鼠氧化应激的影响

目的观察滇白珠水提物干预慢性阻塞性肺疾病(COPD)大鼠超氧化物歧化酶(SOD)活力和丙二醛(MDA)浓度的变化,探讨其在COPD中的作用机制。方法选取雄性SD大鼠36只,将其随机分为对照组、模型组和用药组,各12只。用药组在模型组基础上于每天吸烟前利用灌胃针灌滇白珠水提物,对照组则在模型组基础上灌等量0.9%氯化钠溶液。观察3组大鼠肺组织形态学变化,以及肺组织及肺泡灌洗液(BALF)中SOD、MDA表达情况。结果对照组肺组织和BALF中SOD浓度高于用药组,用药组SOD浓度高于模型组(P0.05);模型组肺组织和BALF中MDA浓度高于用药组,用药组MDA浓度高于对照组(P0.05)。结论滇白珠水提物可降低COPD大鼠SOD、MDA的表达,对COPD的防治有一定指导意义。     

氧化应激与慢性阻塞性肺疾病

氧化/抗氧化失衡导致的氧化应激是慢性阻塞性肺疾病（COPD）重要发病机制之一。许多研究发现在COPD患者和吸烟的气道、呼出气、血液和尿中都有氧化应激标志物水平的明显增高。氧化应激会直接损伤气道上皮,能够使抗蛋白水解酶失活,加重肺部微血管中中性粒细胞的聚集,激活氧化还原敏感的转录因子如核因子-κB和激活蛋白-1而使致炎因子基因的表达增加,加剧COPD患者肺部的炎症反应。COPD患者中的氧化负荷主要来源于香烟烟雾中的氧化物、气道和血液中白细胞释放活性氧物质（ROS）的增多和大气污染。氧化应激和抗氧化物的不足有关,补充抗氧化物可能会减轻氧化应激,所以在COPD的治疗中使用有较好生物活性的抗氧化物或具有抗氧化酶活性的物质可能会减轻氧化应激,最终减轻炎症反应。本文就氧化应激在COPD发病中的作用、抗氧化治疗在COPD治疗中的作用等方面的研究进展作一综述。     

慢性阻塞性肺疾病急性期凝血纤溶系统功能变化的临床研究

目的探讨慢性阻塞性肺疾病(COPD)凝血纤溶功能异常的可能机制。方法选择北京朝阳医院2006—2007年慢性阻塞性肺疾病急性期(AECOPD)住院患者38例,并选择同期47名健康体检者做对照,入选者采用酶联免疫吸附试验(ELISA)测定血浆血管性血友病因子(vWF)、组织因子(TF)、组织因子途径抑制物(TFPI)、凝血因子X、血栓调节蛋白(TM)、蛋白C、组织型纤溶酶原激活物(tPA)、纤溶酶原激活剂抑制物-1(PAI-1)及D-二聚体(D-dimer),发色底物法测定抗凝血酶Ⅲ(AT-Ⅲ)。测定AECOPD患者血气分析、血常规、血脂、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)及血浆纤维蛋白原(FBG)等指标。结果与对照组比较,AECOPD患者vWF、TF、凝血因子Ⅹ、D-dimer及tPA显著升高(P<0.01);TM及蛋白C显著下降(P<0.01)。而两组的AT-Ⅲ、TFPI及PAI-1比较,差异无统计学意义。结论AECOPD患者存在显著凝血纤溶功能失衡状态,在诊治AECOPD患者时,要充分考虑到患者存在的凝血纤溶功能异常,要注意监测相关凝血纤溶指标,对防治AECOPD有重要意义。     

慢性阻塞性肺疾病患者对氧磷酶和氧化应激与全身炎性反应的研究

目的 探讨慢性阻塞性肺疾病(COPD)患者在急性期与稳定期血清对氧磷酶(PoN1)的变化及其与氧化应激、全身炎性反应的关系. 方法 对38例COPD患者在急性期和稳定期血清的PON1活性采用乙酸苯酯法检测,改良Hafeman法检测血清谷胱甘肽过氧化物酶(GSH-Px)活性,比色法测定总抗氧化能力(TAC),硫代巴比妥酸显色法测定丙二醛(MDA)水平,放射免疫法测定血清白介素6(IL-6)和白介素-8(IL-8)水平,免疫投射比浊法测定血清C反应蛋白(CRP)含量. 结果 COPD急性期患者血清PON1活性(98.03±42.40)×103U/L显著低于健康对照组的(136.00±60.50)×103U/L(t=4.962,P<0.01),COPD急性期患者PONl活性与IL-8水平呈显著负相关(r=0.589,P<0.01),与FEV1%呈正相关(r=0.434,P<0.05);GSH-Px活性与IL-6水平呈负相关(r=-0.362,P<0.05);COPD稳定期患者血清PONl活性(131.50±53.65)×103U/L与健康对照组(136.00±60.50)×103U/L比较,差异无统计学意义(t=2.457,P0.05),GSH-Px活性与IL-8水平呈负相关(r=-0.563,P<0.05). 结论 COPD急性期患者PON1活性明显降低,与FEV1%存在正相关,且氧化应激与全身炎性反应之间密切相关.     

慢性阻塞性肺疾病患者骨骼肌功能障碍与氧化应激

近年来慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)的全身表现引起关注,尤其是营养不良、体质量减轻、骨骼肌功能障碍等与COPD患者预后密切相关.氧化应激不但是COPD的发病机制之一,也是导致其骨骼肌功能障碍的重要原因,而运动本身可以诱发和加重COPD患者局部和全身的氧化应激,使病情复杂化.抗氧化治疗是COPD治疗的新靶点,为COPD的运动康复治疗带来了新课题.     

慢性阻塞性肺疾病患者对氧磷酶和氧化应激与全身炎性反应的研究

Objective To analyze the activity of paraoxonase (PON1) and explore the relationship of PON1 and oxidative stress with systemic inflammation response in the acute exacerbation phase and stationary phase in patients with chronic obstructive pulmonary disease (COPD). Methods Serum PON1 activity was measured by phenylacetate in 38 patients with COPD and 30 healthy people. The activity of glutathione peroxidase (GSH-Px) was detected by improved Hafeman method. Total antioxidant capacity (TAC) was measured by eolorimetry and malondialdehyde (MDA) level was measured by thiobarbituric acid colouration method. The interleukin-6 (IL-6) and interleukin-8 (IL-8) levels were detected by radioimmunoassay. The level of C-reactive protein (CRP) was measured by immune turbidimetry. Results In the acute exacerbation phase, the activity of serum PON1 was significantly lower in COPD group than in control group [(98.03±42.40)×103U/L vs. (136.00±60. 50)×103U/L, t=4.962, P<0.01], and it was negatively related to the IL-8 level (r= - 0. 589, P<0.01) and positively related to FEV1% (r= 0. 434, P<0. 05). The activity of GSH-Px was negatively related to the IL-6 level (r=-0. 362, P< 0. 05). In the stationary phase of COPD group, the activity of serum PON1 had no statistical difference compared with control group[(131.50±53.65))×103U/L vs. (136. 00±60.50)×103U/ L, t=2. 457, P>0. 053, and it was negatively related to the IL-8 level (r=-0. 563, P<0.05). Conclusions Serum PON1 activity is significantly decreased in acute exacerbation phase of COPD group compared with control group and it is positively related to FEV1%. The oxidative stress is closely related to systemic inflammation response in patients with acute exacerbation of COPD.     

慢性阻塞性肺疾病患者对氧磷酶和氧化应激与全身炎性反应的研究

Objective To analyze the activity of paraoxonase (PON1) and explore the relationship of PON1 and oxidative stress with systemic inflammation response in the acute exacerbation phase and stationary phase in patients with chronic obstructive pulmonary disease (COPD). Methods Serum PON1 activity was measured by phenylacetate in 38 patients with COPD and 30 healthy people. The activity of glutathione peroxidase (GSH-Px) was detected by improved Hafeman method. Total antioxidant capacity (TAC) was measured by eolorimetry and malondialdehyde (MDA) level was measured by thiobarbituric acid colouration method. The interleukin-6 (IL-6) and interleukin-8 (IL-8) levels were detected by radioimmunoassay. The level of C-reactive protein (CRP) was measured by immune turbidimetry. Results In the acute exacerbation phase, the activity of serum PON1 was significantly lower in COPD group than in control group [(98.03±42.40)×103U/L vs. (136.00±60. 50)×103U/L, t=4.962, P<0.01], and it was negatively related to the IL-8 level (r= - 0. 589, P<0.01) and positively related to FEV1% (r= 0. 434, P<0. 05). The activity of GSH-Px was negatively related to the IL-6 level (r=-0. 362, P< 0. 05). In the stationary phase of COPD group, the activity of serum PON1 had no statistical difference compared with control group[(131.50±53.65))×103U/L vs. (136. 00±60.50)×103U/ L, t=2. 457, P>0. 053, and it was negatively related to the IL-8 level (r=-0. 563, P<0.05). Conclusions Serum PON1 activity is significantly decreased in acute exacerbation phase of COPD group compared with control group and it is positively related to FEV1%. The oxidative stress is closely related to systemic inflammation response in patients with acute exacerbation of COPD.     

慢性阻塞性肺疾病患者对氧磷酶和氧化应激与全身炎性反应的研究

Objective To analyze the activity of paraoxonase (PON1) and explore the relationship of PON1 and oxidative stress with systemic inflammation response in the acute exacerbation phase and stationary phase in patients with chronic obstructive pulmonary disease (COPD). Methods Serum PON1 activity was measured by phenylacetate in 38 patients with COPD and 30 healthy people. The activity of glutathione peroxidase (GSH-Px) was detected by improved Hafeman method. Total antioxidant capacity (TAC) was measured by eolorimetry and malondialdehyde (MDA) level was measured by thiobarbituric acid colouration method. The interleukin-6 (IL-6) and interleukin-8 (IL-8) levels were detected by radioimmunoassay. The level of C-reactive protein (CRP) was measured by immune turbidimetry. Results In the acute exacerbation phase, the activity of serum PON1 was significantly lower in COPD group than in control group [(98.03±42.40)×103U/L vs. (136.00±60. 50)×103U/L, t=4.962, P<0.01], and it was negatively related to the IL-8 level (r= - 0. 589, P<0.01) and positively related to FEV1% (r= 0. 434, P<0. 05). The activity of GSH-Px was negatively related to the IL-6 level (r=-0. 362, P< 0. 05). In the stationary phase of COPD group, the activity of serum PON1 had no statistical difference compared with control group[(131.50±53.65))×103U/L vs. (136. 00±60.50)×103U/ L, t=2. 457, P>0. 053, and it was negatively related to the IL-8 level (r=-0. 563, P<0.05). Conclusions Serum PON1 activity is significantly decreased in acute exacerbation phase of COPD group compared with control group and it is positively related to FEV1%. The oxidative stress is closely related to systemic inflammation response in patients with acute exacerbation of COPD.     

慢性阻塞性肺疾病患者对氧磷酶和氧化应激与全身炎性反应的研究

Objective To analyze the activity of paraoxonase (PON1) and explore the relationship of PON1 and oxidative stress with systemic inflammation response in the acute exacerbation phase and stationary phase in patients with chronic obstructive pulmonary disease (COPD). Methods Serum PON1 activity was measured by phenylacetate in 38 patients with COPD and 30 healthy people. The activity of glutathione peroxidase (GSH-Px) was detected by improved Hafeman method. Total antioxidant capacity (TAC) was measured by eolorimetry and malondialdehyde (MDA) level was measured by thiobarbituric acid colouration method. The interleukin-6 (IL-6) and interleukin-8 (IL-8) levels were detected by radioimmunoassay. The level of C-reactive protein (CRP) was measured by immune turbidimetry. Results In the acute exacerbation phase, the activity of serum PON1 was significantly lower in COPD group than in control group [(98.03±42.40)×103U/L vs. (136.00±60. 50)×103U/L, t=4.962, P<0.01], and it was negatively related to the IL-8 level (r= - 0. 589, P<0.01) and positively related to FEV1% (r= 0. 434, P<0. 05). The activity of GSH-Px was negatively related to the IL-6 level (r=-0. 362, P< 0. 05). In the stationary phase of COPD group, the activity of serum PON1 had no statistical difference compared with control group[(131.50±53.65))×103U/L vs. (136. 00±60.50)×103U/ L, t=2. 457, P>0. 053, and it was negatively related to the IL-8 level (r=-0. 563, P<0.05). Conclusions Serum PON1 activity is significantly decreased in acute exacerbation phase of COPD group compared with control group and it is positively related to FEV1%. The oxidative stress is closely related to systemic inflammation response in patients with acute exacerbation of COPD.     

慢性阻塞性肺疾病患者氧化应激与肺功能的相关性

目的探讨COPD患者氧化应激状态以及对肺功能的影响。方法选择COPD患者88例,行肺功能测定,根据FEV1%及FEV1/FVC分为轻、中、重三组,并对所有入选者抽取静脉血,化学比色法检测血清还原型谷胱甘肽(GSH)、丙二醛(MDA)、超氧化物歧化酶(SOD)的水平。结果与轻度组比较,中、重度COPD患者SOD、GSH水平明显下降,MDA明显升高(P<0.05、P<0.01)。相关分析显示:MDA与肺功能(FEV1%、FEV1/FVC)呈负相关(P<0.01、P<0.05),SOD、GSH与肺功能呈正相关(P<0.01、P<0.05)。结论 COPD患者体内存在氧化应激失衡,随着氧化/抗氧化功能失衡加重,肺功能下降加剧。     

稳定期慢性阻塞性肺疾病患者的合并症情况与CAT评分之间关系的研究

目的研究稳定期慢性阻塞性肺疾病(COPD)患者的合并症与COPD评估测试(CAT)评分之间的关系.方法纳入2018年3月至2019年3月于长春市二级医院(4家)、三级医院(4家)门诊就诊的400例稳定期COPD患者,填写统一调查问卷,对问卷中患者的合并症及CAT评分进行统计分析.结果实际完成有效调查问卷389份,主要合并症分别为:缺血性心脏病148例(38.05%)、高血压病109例(28.02%)、支气管哮喘79例(20.31%)、糖尿病40例(10.28%)、支气管扩张36例(9.25%)、慢性心功能不全35例(9.00%);合并症个数为0个(108例)、1个(141例)、≥2个(140例)时患者的CAT评分分别为(15.99±7.35)分、(19.45±7.10)分、(20.23±7.91)分,3组不同合并症个数患者的CAT评分差异有统计学意义(F=10.733,P<0.05),分别有0个、1个合并症患者的CAT评分差异有统计学意义(t=3.620,P<0.05),分别有0个、≥2个合并症患者的CAT评分差异有统计学意义(t=4.432,P<0.05).根据有无特定合并症分类,合并及不合并支气管哮喘者CAT评分差异有统计学意义[(20.56±6.90)分比(18.31±7.78)分,t=-2.340,P<0.05];合并及不合并缺血性心脏病者CAT评分差异有统计学意义[(20.47±7.45)分比(17.72±7.60)分,t=-3.492,P<0.05];合并及不合并慢性心功能不全者CAT评分差异有统计学意义[(21.46±7.74)分比(18.50±7.60)分,t=-2.190,P<0.05].结论稳定期COPD患者的合并症个数越多,患者的CAT评分越高,生活质量越差,其中支气管哮喘、缺血性心脏病、慢性心功能不全对患者的生活质量影响显著.     

稳定期慢性阻塞性肺疾病患者的去脂质量指数与骨强度的关系

目的 探讨稳定期慢性阻塞性肺疾病(慢阻肺)患者的去脂质量指数与骨强度关系.方法 纳入2013年3月至2014年1月的稳定期慢阻肺患者94例及健康吸烟者47名,所有受试者均为男性,其中慢阻肺组年龄45～79岁,平均(65±7)岁,对照组年龄40～79岁,平均(58±9)岁.测定肺功能、机体构成及骨强度,采用慢阻肺评估测试中文版问卷、mMRC量表评价慢阻肺患者症状、记录其最近12个月急性加重次数及因此住院次数并进行比较.正态分布数据用均数±标准差、非正态分布数据用中位数(四分位数间距)表示.符合正态分布的数据,若方差齐,采用t检验进行两组间比较;若方差不齐,则采用t’检验进行两组间比较.结果 稳定期慢阻肺组患者合并肌肉萎缩[去脂质量指数(FFMI)＜ 16 kg/m2]和骨折高风险[骨强度指数(SI)T＜-1]的发生率分别为24.5％ (23/94)和72.3％(68/94).合并肌肉萎缩的慢阻肺患者与肌肉体积正常的患者相比,FEV1占预计值％降低[(39±15)％,(50±16)％]、最近12个月急性加重次数增加[1.0(0～3.0),0(0～1.0)]、骨强度指数降低[(76±13)％,(86±16)％,t值和t’值分别为2.904,-1.476,2.728,均P＜0.05],存在骨折高风险的慢阻肺患者与骨折低风险的患者相比,mMRC评分增加[2.0(1.0 ～3.0)和1.0(0～2.0)](Z值为-2.297,P＜0.05).慢阻肺患者去脂指数与骨强度指数呈正相关(r=0.294,P＜0.05).结论 合并肌肉萎缩和骨折高风险的稳定期男性慢阻肺患者肺功能降低,未来急性加重风险增加,二者呈正相关,慢阻肺患者应注意筛查上述合并症.     

无症状慢性阻塞性肺疾病患者特点分析

目的了解北京市农村地区无症状慢性阻塞性肺疾病(COPD)患者的流行病学特点。方法对北京市延庆县5个自然村40岁以上1624名进行入户调查。进行问诊、体检,填写流行病学调查问卷并进行肺功能检查。结果该地区40岁以上COPD患者148例,总患病率为9.1%(148/1624),其中无症状组62例(42%),有症状组86例(58%);无症状COPD的患病率为3.8%(62/1624)。无症状组和有症状组患者性别、年龄、职业、婚姻状况、受教育程度和吸烟情况比较差异均无统计学意义(P均>0.05)。肺功能检测显示,有症状组第一秒用力呼气容积(FEV1)、第一秒用力呼气容积占预计值百分比(FEV1占预计值%)为(1.3±0.7)L、(61±23)%,与无症状组[(1.5±0.6)L、(70±22)%]比较,差异均有统计学意义(P均<0.05)。结论COPD在该地区患病率较高,其中无症状COPD的比例也较高。由于COPD的诊断需要依靠肺功能测定,而早期肺功能受损不太严重时临床症状不明显,因而造成COPD的漏诊和对疾病危害的低估。     

稳定期慢性阻塞性肺疾病患者的气道阻力与运动相关呼吸困难肺功能参数的关系

目的观察稳定期慢性阻塞性肺疾病(COPD)患者的各项气道阻力(Raw)参数与运动相关呼吸困难肺功能参数的相关关系。方法前瞻性纳入上海交通大学附属胸科医院和第一人民医院门诊稳定期COPD患者180例,根据慢性阻塞性肺疾病全球倡议(GOLD 2017版)制订的肺功能诊断标准分为Ⅰ-Ⅳ级4组,受试前8 h内均未应用支气管舒张剂。所有患者在吸入沙丁胺醇400μg后接受常规肺功能和气道阻力测试。同期选择42例成年健康体检者作为对照组。结果Ⅱ级以上COPD患者的第1秒用力呼气容积和呼出50%肺活量时流量均显著低于健康成年人和Ⅰ级COPD患者,总气道阻力、有效气道阻力、吸气阻力和呼气阻力则呈进行性增高。Ⅲ-Ⅳ级COPD患者的深吸气量占预计值百分比(IC%pred)<80%,同时改良英国医学研究委员会呼吸困难量表评分超过2分;7例Ⅲ级(13.2%)和14例Ⅳ级COPD患者(33.3%)的吸气分数(IC/TLC)≤25%,而仅有1例Ⅱ级COPD患者的IC/TLC≤25%(1.9%)。结论稳定期中重度COPD患者呼出气流受限趋于加重,Raw各项参数中呼气阻力增高尤为显著。Ⅲ-Ⅳ级COPD患者更易出现运动相关呼吸困难症状,且IC/TLC≤25%。     

内源性硫化氢在慢性阻塞性肺疾病患者中的变化及意义

目的研究内源性硫化氢(H2S)在慢性阻塞性肺疾病(COPD)发病中的作用。方法COPD急性加重组(AECOPD组)27例、稳定期COPD组37例和健康对照组13名,在入选时测定血清H2S和一氧化氮(NO)水平、肺功能、诱导痰细胞分类计数,对AECOPD患者行超声心动图和血气分析。结果(1)血清H2S水平稳定期COPD组[(50·8±2·5)μmol/L]比健康对照组[(39·8±1·6)μmol/L]、AECOPD组[(33·5±2·2)μmol/L]均显著增加(P均<0·01)。(2)AECOPD组吸烟者血清H2S[(28·1±1·3)μmol/L]比非吸烟者[(39·4±3·9)μmol/L,P<0·05]和健康非吸烟者显著降低[(39·8±1·6)μmol/L,P<0·01]。(3)稳定期COPD组不同程度气流阻塞患者血清H2S水平呈线性下降趋势(P<0·05),COPD全球创议(GOLD)Ⅲ期[(45·1±4·1)μmol/L]较Ⅰ期患者[(70·2±6·2)μmol/L]血清H2S水平显著下降(P<0·05)。(4)AECOPD组伴有肺动脉高压患者血清H2S水平显著降低[(26·3±2·2)、(36·2±2·5)μmol/L,P<0·05]。(5)血清H2S与NO、第一秒用力呼气容积占预计值百分比(FEV1占预计值%)、诱导痰淋巴细胞计数、诱导痰巨噬细胞计数均呈正相关(r=0·278~0·533,P均<0·05或0·01),与肺动脉收缩压(PASP)、诱导痰中性粒细胞计数均呈负相关(r=-0·561、-0·422,P=0·011、0·001)。结论内源性H2S可能参与COPD气流阻塞的发病,作为一种无创指标监测疾病严重程度和活动度具有一定意义。     

内质网应激在慢性阻塞性肺疾病中的研究进展

内质网应激(ERS)是细胞的一种重要自我防御机制,而强烈持久的ERS可导致细胞凋亡。未折叠蛋白反应是ERS的一条重要信号通路。支气管、肺泡上皮等细胞内含多种蛋白质合成分泌旺盛的细胞类型,本身易出现ERS;目前认为ERS与慢性阻塞性肺疾病(COPD)发病机制有一定关系。本文即对ERS与COPD的相关研究作一综述,希望为COPD的治疗提供新的方向。