慢性阻塞性肺疾病合并肺动脉高压患者血清活性氧和硫化氢水平及肺组织还原型烟酰胺腺嘌呤二核苷酸氧化酶-4和胱硫醚-γ-裂解酶表达及其意义  

Expression of nicotinamide adenine dinucleotide phosphate-reduced oxidase-4/reactive oxygen species and cystathionine-γ-lyase/hydrogen sulfide in patients with chronic obstructive pulmonary disease-related pulmonary hypertension

作　　者：袁雪枚 耑冰[1] 李萍[1] 赵霞 汪涛 杨朝 Yuan Xuemei;Zhuan Bing;Li Ping;Zhao Xia;Wang Tao;Yang Zhao(Department of Respiratory Medicine People's Hospital of Ningxia Hui Autonomous Regin,Yinchuan 750011,China;Department of Respiratory and Critical Care,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Respiratory Medicine,Suzhou Science and Technology Town Hospital,Suzhou 215153,China)

机构地区：[1]宁夏回族自治区人民医院总院呼吸内科,银川750011 [2]华中科技大学同济医学院同济医院呼吸与危重症科,武汉430030 [3]苏州科技城医院呼吸科,215153

出　　处：《中华内科杂志》2019年第10期770-776,共7页Chinese Journal of Internal Medicine

基　　金：国家自然科学基金(81160011、81560014、81470252);宁夏回族自治区2017年度留学人员创新创业项目(宁人社函[2017]84号);宁夏回族自治区重点研发计划项目(2018BEG03052、2018BEG03054).

摘　　要：目的探讨慢性阻塞性肺疾病(COPD)急性加重期患者血清活性氧(ROS)、硫化氢(H2S)水平,及COPD 稳定期患者肺组织中还原型烟酰胺腺嘌呤二核苷酸(NADPH)氧化酶-4 (NOX4)、胱硫醚-γ-裂解酶(CSE)表达及其意义.方法(1)选2015年11月至2016年12月在宁夏回族自治区人民医院呼吸科住院的COPD急性加重患者60例,根据是否合并肺动脉高压(PH)分为COPD急性加重合并PH组和COPD急性加重未合并PH组,另选同期健康体检者30例为健康对照组,采用酶联免疫法测3组受试者血清ROS、H2S水平.(2)收集2012年11月至2017年4月在宁夏回族自治区人民医院心胸外科因肺癌行肺叶切除42例患者的肺组织,根据是否合并PH分为COPD稳定期合并PH组和COPD稳定期未合并PH组、对照组,免疫组化法测3组患者肺组织NOX4、CSE表达,并观察肺小动脉壁厚度.结果(1)COPD急性加重合并PH组患者血清ROS水平[(613.52± 69.66)IU/ml]高于COPD急性加重未合并PH组[(565.76±71.33)IU/ml]、健康对照组[(294.63±60.39) IU/ml],COPD急性加重未合并PH组患者血清ROS水平高于健康对照组(P<0.05).COPD急性加重合并PH组患者血清H2S水平[(18.59±5.50)nmol/ml]低于COPD急性加重未合并PH组[(20.49± 4.97)nmol/ml]、健康对照组[(38.03±4.43)nmol/ml],COPD急性加重未合并PH组患者血清H2S水平低于健康对照组(P<0.05).ROS水平与肺动脉收缩压(PASP)呈正相关(r=0.59,P<0.05),H2S水平与PASP呈负相关(r=-0.62,P<0.05).(2)COPD稳定期合并PH组肺组织NOX4表达(0.08±0.01)高于COPD稳定期未合并PH组(0.06±0.01)、对照组(0.03±0.01),COPD稳定期未合并PH组肺组织NOX4表达高于对照组(P<0.05).COPD稳定期合并PH组肺组织CSE表达(0.03±0.01)低于COPD稳定期未合并PH组(0.07±0.02)、对照组(0.12±0.02),COPD稳定期未合并PH组肺组织CSE表达低于对照组(P<0.05). COPD稳定期合并PH组WT%[(40.58±6.63)%]高于COPD稳定期未合并PH组[(36.87±5.60)%]、对照组[(31.27±6.24)%],COPD稳定期�Objective To observe the levels of serum reactive oxygen species (ROS) and hydrogen sulfide(H2S) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and nicotinamide adenine dinucleotide phosphate-reduced (NADPH) oxidase 4 (NOX4) and cystathionine-γ-lyase (CSE) in lung tissue of patients with stable chronic obstructive pulmonary disease (COPD). Methods (1) A total of 60 patients with AECOPD admitted to the Department of Respiratory Medicine at Ningxia Hui People′s Hospital from November 2015 to December 2016 were recruited. According to the results of pulmonary function and echocardiography, the participants were divided into AECOPD-related pulmonary hypertension (PH) group(A) and AECOPD non-PH group (B).Other 30 healthy subjects were selected as the control group (C).Serum ROS and H2S of group A, B and C were detected by enzyme-linked immunosorbent assay (ELISA).(2)The lung tissues of patients undergoing lobectomy for lung cancer from November 2012 to April 2017 were collected, who were divided into COPD-related PH group (D), COPD non-PH group (E) and negative control (F). The expression of NOX4 and CSE protein in lung tissue was detected by immunohistochemistry and the thickness of pulmonary arteriole wall was measured. Results (1)The serum ROS level in group A was higher than group B and C which were (613.52±69.66)IU/ml,(565.76±71.33)IU/ml,(294.63±60.39)IU/ml, respectively with that in group B higher than that in group C (P<0.05). Serum H2S level in group A was lower than group B and C, with that in group B lower than group C [(18.59±5.50) nmol/ml,(20.49±4.97) nmol/ml,(38.03±4.43) nmol/ml, respectively P<0.05]. ROS level was positively correlated with pulmonary systolic pressure (PASP)(r=0.59, P<0.05), H2S level was negatively correlated with PASP(r=-0.62, P<0.05).(2)The lung tissue expression of NOX4 in group D was higher than group E and F (P<0.05), which were 0.08±0.01,0.06±0.01,0.03±0.01, respectively,while the level of NOX4 in group E was higher than group F

关 键 词：肺疾病 慢性阻塞性 高血压 肺性 还原型烟酰胺腺嘌呤二核苷酸氧化酶-4 活性氧 硫化氢 胱硫醚-Γ-裂解酶 

分 类 号：R563.9[医药卫生—呼吸系统] R544.1[医药卫生—内科学]