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
10.3760/cma.j.issn.0578-1426.2019.10.009
- VernacularTitle: 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
- Author:
Xuemei YUAN
1
;
Bing ZHUAN
1
;
Ping LI
1
;
Xia ZHAO
1
;
Tao WANG
2
;
Zhao YANG
3
Author Information
1. Department of Respiratory Medicine People's Hospital of Ningxia Hui Autonomous Regin, Yinchuan 750011, China
2. Department of Respiratory and Critical Care, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
3. Department of Respiratory Medicine, Suzhou Science and Technology Town Hospital, Suzhou 215153, China
- Publication Type:Journal Article
- Keywords:
Pulmonary disease, chronic obstructive;
Hypertension, pulmonary;
Nicotinamide adenine dinueleotide phosphate-reduced oxidase 4;
Reactive oxygen species;
Hydrogen sulfide;
Cystathionine-γ
-lyase
- From:
Chinese Journal of Internal Medicine
2019;58(10):770-776
- CountryChina
- Language:Chinese
-
Abstract:
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 (P<0.05). The expression of CSE between group D, E and F were all significantly different (P<0.05),which were 0.03±0.01, 0.07±0.02,0.12±0.02, respectively.(3)Smooth muscle thickness of pulmonary arterioles as a percentage of vascular diameter (WT%) between group D, E and F was all different(P<0.05), which were (40.58±6.63)%,(36.87±5.60)%,(31.27±6.24)%, respectively; so was smooth muscle area of pulmonary arterioles as a percentage of total vascular area(WA%) with (32.33±6.27)%, (30.20±5.28)%, (25.20±4.31)%, respectively (P<0.05). (4)The expression of NOX4 was positively correlated with WT% and WA%, r was 0.81 and 0.66, respectively (P<0.05). The expression of CSE was negatively correlated with WT% and WA%, r was -0.55 and -0.39 respectively (P<0.05).
Conclusions:NOX4/ROS and CSE/H2S signaling pathways may play an important role in the pathogenesis of COPD related PH.
