摘要目的 探索慢性阻塞性肺疾病(慢阻肺)肺小动脉重塑情况,观察其对近端肺动脉血液流变学、右心室结构和功能的影响及机制.方法 回顾性分析2016年9月至2017年3月宁夏医科大学总医院收治的因肺部肿瘤行手术治疗的患者共34例,其中男25例,女9例,年龄40～65岁,平均(56±8)岁.根据术前肺功能分为慢阻肺合并肺部肿瘤组(慢阻肺组)15例及肺功能正常合并肺部肿瘤组(对照组)19例.所有纳入患者术前接受心脏核磁共振扫描获取近端肺动脉血液流变学、右心室结构及功能改变.术中取病变周围正常的肺组织采用HE、改良Weigert弹力纤维染色观察肺小动脉形态学改变;免疫组化检测肺小动脉 α-平滑肌肌动蛋白(α-SMA)、增殖细胞核抗原(PCNA)定位及表达;免疫印迹和实时荧光定量PCR检测肺组织 α-SMA蛋白及mRNA表达水平.结果 慢阻肺组与对照组平均肺动脉压(mPAP)分别为(24.0±3.7)和(22.8±1.6)mmHg(1 mmHg=0.133 kPa),组间比较差异无统计学意义(P>0.05).慢阻肺组主肺动脉扩张度(mPAD％)为(44±11)％,低于对照组[(57±14)％,P<0.05];慢阻肺组肺小动脉平滑肌厚度(WT)、平滑肌厚度占血管外径百分比(WT％)及平滑肌面积占血管总面积百分比(WA％)分别为(37±18)μm、(65±19)％和(55±23)％,均高于对照组[(19±3)μm、(29±5)％和(40±7)％,均P<0.05].右心室舒张末期(RVMED)、收缩末期心肌质量(RVMES)、平均反向流量(ANF)及反流分数(RF％)均高于对照组(均P<0.05),单位面积肺小动脉平滑肌细胞数及细胞增殖率较对照组增高(均P<0.01).慢阻肺组肺组织免疫组化 α-SMA蛋白和mRNA表达高于对照组(均P<0.05).相关分析结果显示WA％、WT％与mPAD呈负相关,与RVMES、RVMED、RF％呈正相关.结论 在尚未出现肺动脉高压的情况下,慢阻肺患者已存在以小动脉重塑和肺动脉血液流变学改变为特征的血管病变及右心心肌的结构改变,且小动脉重塑影响主肺动脉血液流变学改变进而影响右心心肌结构改变.

abstractsObjective To explore the remodeling of pulmonary arterioles in chronic obstructive pulmonary disease (COPD), and its effect on hemorheology of proximal pulmonary arteries , right ventricular structure and function ,and the potential mechanisms.Method A total of 34 patients undergoing surgical treatment for lung tumors admitted to the General Hospital of Ningxia Medical University were included in the study.According to the preoperative lung function , there were 15 patients with COPD complicated with lung tumor (COPD group) and 19 patients with normal pulmonary function with lung tumor (control group).All patients underwent cardiac nuclear magnetic resonance (CMR) before surgery, and the hemorheology of the proximal pulmonary arteries, right ventricular structure and function were obtained by CMR .The normal lung tissues distal to the tumor lesion were taken during the operation , and the morphological changes of the pulmonary arterioles were observed by hematoxylin -eosin staining and Weigert-van Gieson. Immunohistochemistry was used to detect the location and expression of α-smooth muscle actin(SMA) and proliferating cell nuclear antigen(PCNA) in pulmonary arterioles, and the expression of protein and mRNA of α-SMA in lung tissue was detected by Western -blotting and real-time quantitative PCR.Results The results of CMR showed that mPAP was not statistically different between COPD group and control group (24.0 ±3.7 vs 22.8 ±1.6, P >0.05) .The main pulmonary artery distensibility ( mPAD％), right ventricular myocardial mass end-diastolic ( RVMED ), right ventricular myocardial mass end-systolic (RVMES), average negative flow(ANF) and regurgitant fraction(RF％) were statistically different between COPD group and control group (P <0.05).The wall thickness (WT), WT％ and WA％ were significantly higher in COPD group [(37 ±18) μm, (65 ±19)％ and (55 ±23)％, respectively] than in control group [(19 ±3 ) μm, (29 ±5)％ and (40 ±7)％, respectively] .The number of pulmonary arterial smooth muscle cells per unit area and smooth muscle cell proliferation rate were significantly higher in COPD group than in the control group (P <0.01).The expression of α-SMA protein and mRNA in COPD group was higher than that in control group (P <0.05).WA％ and WT％ were correlated inversely with mPAD％, but positively with RVMES, RVMED and RF％.Conclusions Pulmonary vascular remodeling and rheological changes, even right heart myocardial structural changes , were observed in COPD patients without pulmonary arterial hypertension.Pulmonary arteriolar remodeling can affect the main pulmonary arterial hemorheology in COPD patients and further affect the myocardial structure of right heart .Pulmonary arterial remodeling may be a new direction for the clinical treatment of COPD .