Effects of smoking combined with intermittent hypoxia exposure on the lungs and vascular endothelial function in rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

BI Hong , HUANG Zhaoming , HE Xu , CHEN Min , HE Jian , HE Lewei , GUO Xiang , WANG Liyan , DU Junyi , ZHOU Kaihua , WANG Qing ,  JIN Zhixian

Department of Pneumology, the First Hospital of Kunming Almette Hospital, Kunming, Yunnan 650224, P. R. China;

Corresponding author：

JIN Zhixian, Email: jzx666999@163.com

Keywords：

Smoking; Emphysema; Intermittent hypoxia; Obstruction; Sleep apnea hypopnea; Overlap; Endothelium; Rat

DOI：

10.7507/1671-6205.201809021

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effects of smoking combined with intermittent hypoxia on the pathophysiology of lung tissue and thoracic aorta, and the endothelial injury.Methods Twenty-four rats (SPF, female, six weeks old) were divided randomly into 4 groups (n=6). The control group was given false smoking and normal oxygen exposure, the smoking-exposed group was exposed in smoking, the intermittent hypoxia group was exposed in intermittent hypoxia environment, and the overlap group was exposed to smoking and intermittent hypoxia. After 8 weeks, body weight, right ventricular hypertrophy index (RVHI), the pathological changes of lung tissue and thoracic aorta were measured, and the level of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1α (SDF-1α) in serum of rats were evaluated.Results RVHI of rats in the smoking-exposed group, intermittent hypoxia group, overlap group were higher than that in the control group. In addition, RVHI in the overlap group was higher than that in the smoking-exposed group, intermittent hypoxia group (all P<0.05). The levels of ET-1, VEGF and SDF-1α in the serum of the smoking-exposed group, intermittent hypoxia group and overlap group were higher than those in the control group, while the level of eNOS was lower than that in the control group, (all P<0.05), the most significant difference was between control group and the overlap group. Pathological observation of lung tissue and thoracic aorta showed obvious emphysema in the smoking-exposed group and overlap group, which was more obvious in the overlap group than that in the smoking-exposed group (all P<0.05). Lung interstitial inflammatory infiltration, bronchial wall lymphocyte hyperplasia and pulmonary fibrosis were shown in different degrees in the smoking-exposed group, intermittent hypoxia group and overlap group, and the pulmonary arteriole wall showed thickening, fibrosis and peripheral inflammatory infiltration also were found in these groups. Thoracic aorta in the smoking-exposed group, intermittent hypoxia group and overlap group showed different degrees of endothelial cell injury, middle membrane thickening, and collagen fiber hyperplasia. The pathological features of the overlap group were most obvious compared to the other two groups.Conclusions Smoking and intermittent hypoxia exposure can lead to different degrees of lung tissue and vascular endothelial injury and decrease of vascular endothelial protective factors in rats, resulting in dysfunction of vascular endothelial cells, which leads to the structural remodeling of pulmonary arterioles and aorta, such as thickening, fibrosis, etc. Combined smoking and intermittent hypoxia exposure can lead to more serious pathological damage.

Citation： BI Hong, HUANG Zhaoming, HE Xu, CHEN Min, HE Jian, HE Lewei, GUO Xiang, WANG Liyan, DU Junyi, ZHOU Kaihua, WANG Qing, JIN Zhixian. Effects of smoking combined with intermittent hypoxia exposure on the lungs and vascular endothelial function in rats. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(6): 560-566. doi: 10.7507/1671-6205.201809021 Copy

1.	Thomashow MA, Shimbo D, Parikh MA, et al. Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease study. Am J Respir Crit Care Med, 2013, 188(1): 60-68.
2.	Feng J, Wang QS, Chiang A, et al. The effects of sleep hypoxia on coagulant factors and hepatic inflammation in emphysematous rats. PLoS One, 2010, 5(10): e13201.
3.	冯靖, 陈宝元, 郭美南, 等. 间歇低氧气体环境模型的建立. 天津医科大学学报, 2006, 12(4): 509-515.
4.	陈敏, 黄照明, 何剑, 等. 通过烟熏和间歇低氧构建大鼠 COPD-OSAHS 重叠综合征模型. 中国实验动物学报, 2019, 27(1): 59-64.
5.	李秀, 吕芳. 慢性阻塞性肺疾病血清内皮素及其临床意义. 安徽医学, 2000, 21(2): 39-40.
6.	张超, 欧敏. 瘦素在间歇低氧致肺动脉内皮损伤中的作用. 海南医学杂志, 2018, 29(14): 1935-1937.
7.	蒋光峰, 张金慧, 李薇. OSAHS 患者血清 NO、VEGF、HIF-1α 水平的变化及临床意义. 临床耳鼻咽喉头颈外科杂志, 2012, 26(18): 807-810.
8.	Zychowski KE, Sanchez B, Pedrosa RP, et al. Serum from obstructive sleep apnea patients induces inflammatory responses in coronary artery endothelial cells. Atherosclerosis, 2016, 254: 59-66.
9.	McNicholas WT. Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease. Am J Respir Crit Care Med, 2009, 180(8): 692-700.
10.	Flenley DC. Sleep in chronic obstructive lung disease. Clin Chest Med, 1985, 6(4): 651-661.
11.	Sanders MH, Newman AB, Haggerty CL, et al. Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease. Am J Respir Crit Care Med, 2003, 167(1): 7-14.
12.	Marin JM, Soriano JB, Carrizo SJ, et al. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med, 2010, 182(3): 325-331.
13.	Neilan TG, Bakker JP, Sharma B, et al. T1 measurements for detection of expansion of the myocardial extracellular volume in chronic obstructive pulmonary disease. Can J Cardiol, 2014, 30(12): 1668-1675.
14.	Sharma B, Neilan TG, Kwong RY, et al. Evaluation of right ventricular remodeling using cardiac magnetic resonance imaging in co-existent chronic obstructive pulmonary disease and obstructive sleep apnea. COPD, 2013, 10(1): 4-10.
15.	Serban KA, Rezania S, Petrusca DN, et al. Structural and functional characterization of endothelial microparticles released by cigarette smoke. Sci Rep, 2016, 6: 31596.
16.	陈云芳, 王胜, 钱自亮. 香烟烟雾法肺动脉高压小鼠模型肺组织 HIF-1α 和 Nrf2 表达. 江西师范大学学报(自然科学版), 2017, 41(2): 155-159.
17.	Sajkov D, Wang T, Saunders NA, et al. Daytime pulmonary hemodynamics in patients with obstructive sleep apnea without lung disease. Am J Respir Crit Care Med, 1999, 159(5 Pt 1): 1518-1526.
18.	毕虹, 金志贤, 周开华, 等. 重叠综合征患者血管内皮损伤机制及靶向治疗进展. 天津医药, 2017, 45(11): 1228-1232.
19.	Kai S, Tanaka T, Daijo H, et al. Hydrogen sulfide inhibits hypoxia-but not a anoxia-induced hypoxia-inducible factor 1 activation in a von Hippel-Lindau-and mitochondria-dependent manner. Antioxid Redox Signal, 2012, 16(3): 203-216.
20.	Paradis A, Zhang L. Role of endothelin in uteroplacental circulation and fetal vascular function. Curr Vasc Pharmacol, 2013, 11(5): 594-605.
21.	罗美蓉, 王正伟, 安志星. 人血管内皮生长因子研究进展. 中国老年学杂志, 2012, 32(17): 3835-3837.
22.	Janssens R, Mortier A, Boff D, et al. Natural nitration of CXCL12 reduces its signaling capacity and chemotactic activity in vitro and abrogates intra-articular lymphocyte recruitment in vivo. Oncotarget, 2016, 7(38): 62439-62459.
23.	Yu Y, Wu RX, Gao LN, et al. Stromal cell-derived factor-1-directed bone marrow mesenchymal stem cell migration in response to inflammatory and/or hypoxic stimuli. Cell Adh Migr, 2016, 10(4): 342-359.
24.	王英, 李亚, 李建生. 慢性阻塞性肺疾病肺血管重塑研究进展. 中医学报, 2012, 27(02): 143-145.
25.	孙艾琦, 孙丽丹, 白丽华, 等. 慢性阻塞性肺疾病与阻塞性睡眠呼吸暂停低通气综合征及重叠综合征患者血管内皮生长因子表达差异. 中华实用诊断与治疗杂志, 2017, 31(3): 262-263.
26.	曹娟, 王滨, 张秀伟, 等. 老年重叠综合征患者血管内皮功能的观察. 中国医药科学, 2011, 1(23): 20-22.

1. Thomashow MA, Shimbo D, Parikh MA, et al. Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease study. Am J Respir Crit Care Med, 2013, 188(1): 60-68.
2. Feng J, Wang QS, Chiang A, et al. The effects of sleep hypoxia on coagulant factors and hepatic inflammation in emphysematous rats. PLoS One, 2010, 5(10): e13201.
3. 冯靖, 陈宝元, 郭美南, 等. 间歇低氧气体环境模型的建立. 天津医科大学学报, 2006, 12(4): 509-515.
4. 陈敏, 黄照明, 何剑, 等. 通过烟熏和间歇低氧构建大鼠 COPD-OSAHS 重叠综合征模型. 中国实验动物学报, 2019, 27(1): 59-64.
5. 李秀, 吕芳. 慢性阻塞性肺疾病血清内皮素及其临床意义. 安徽医学, 2000, 21(2): 39-40.
6. 张超, 欧敏. 瘦素在间歇低氧致肺动脉内皮损伤中的作用. 海南医学杂志, 2018, 29(14): 1935-1937.
7. 蒋光峰, 张金慧, 李薇. OSAHS 患者血清 NO、VEGF、HIF-1α 水平的变化及临床意义. 临床耳鼻咽喉头颈外科杂志, 2012, 26(18): 807-810.
8. Zychowski KE, Sanchez B, Pedrosa RP, et al. Serum from obstructive sleep apnea patients induces inflammatory responses in coronary artery endothelial cells. Atherosclerosis, 2016, 254: 59-66.
9. McNicholas WT. Chronic obstructive pulmonary disease and obstructive sleep apnea: overlaps in pathophysiology, systemic inflammation, and cardiovascular disease. Am J Respir Crit Care Med, 2009, 180(8): 692-700.
10. Flenley DC. Sleep in chronic obstructive lung disease. Clin Chest Med, 1985, 6(4): 651-661.
11. Sanders MH, Newman AB, Haggerty CL, et al. Sleep and sleep-disordered breathing in adults with predominantly mild obstructive airway disease. Am J Respir Crit Care Med, 2003, 167(1): 7-14.
12. Marin JM, Soriano JB, Carrizo SJ, et al. Outcomes in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome. Am J Respir Crit Care Med, 2010, 182(3): 325-331.
13. Neilan TG, Bakker JP, Sharma B, et al. T1 measurements for detection of expansion of the myocardial extracellular volume in chronic obstructive pulmonary disease. Can J Cardiol, 2014, 30(12): 1668-1675.
14. Sharma B, Neilan TG, Kwong RY, et al. Evaluation of right ventricular remodeling using cardiac magnetic resonance imaging in co-existent chronic obstructive pulmonary disease and obstructive sleep apnea. COPD, 2013, 10(1): 4-10.
15. Serban KA, Rezania S, Petrusca DN, et al. Structural and functional characterization of endothelial microparticles released by cigarette smoke. Sci Rep, 2016, 6: 31596.
16. 陈云芳, 王胜, 钱自亮. 香烟烟雾法肺动脉高压小鼠模型肺组织 HIF-1α 和 Nrf2 表达. 江西师范大学学报(自然科学版), 2017, 41(2): 155-159.
17. Sajkov D, Wang T, Saunders NA, et al. Daytime pulmonary hemodynamics in patients with obstructive sleep apnea without lung disease. Am J Respir Crit Care Med, 1999, 159(5 Pt 1): 1518-1526.
18. 毕虹, 金志贤, 周开华, 等. 重叠综合征患者血管内皮损伤机制及靶向治疗进展. 天津医药, 2017, 45(11): 1228-1232.
19. Kai S, Tanaka T, Daijo H, et al. Hydrogen sulfide inhibits hypoxia-but not a anoxia-induced hypoxia-inducible factor 1 activation in a von Hippel-Lindau-and mitochondria-dependent manner. Antioxid Redox Signal, 2012, 16(3): 203-216.
20. Paradis A, Zhang L. Role of endothelin in uteroplacental circulation and fetal vascular function. Curr Vasc Pharmacol, 2013, 11(5): 594-605.
21. 罗美蓉, 王正伟, 安志星. 人血管内皮生长因子研究进展. 中国老年学杂志, 2012, 32(17): 3835-3837.
22. Janssens R, Mortier A, Boff D, et al. Natural nitration of CXCL12 reduces its signaling capacity and chemotactic activity in vitro and abrogates intra-articular lymphocyte recruitment in vivo. Oncotarget, 2016, 7(38): 62439-62459.
23. Yu Y, Wu RX, Gao LN, et al. Stromal cell-derived factor-1-directed bone marrow mesenchymal stem cell migration in response to inflammatory and/or hypoxic stimuli. Cell Adh Migr, 2016, 10(4): 342-359.
24. 王英, 李亚, 李建生. 慢性阻塞性肺疾病肺血管重塑研究进展. 中医学报, 2012, 27(02): 143-145.
25. 孙艾琦, 孙丽丹, 白丽华, 等. 慢性阻塞性肺疾病与阻塞性睡眠呼吸暂停低通气综合征及重叠综合征患者血管内皮生长因子表达差异. 中华实用诊断与治疗杂志, 2017, 31(3): 262-263.
26. 曹娟, 王滨, 张秀伟, 等. 老年重叠综合征患者血管内皮功能的观察. 中国医药科学, 2011, 1(23): 20-22.

Previous Article
Clinical features of anthracosis and bronchial anthracofibrosis
Next Article
A case report of pulmonary lymphomatoid granulomatosis confirmed by autopsy and review of the literature

Chinese Journal of Respiratory and Critical Care Medicine

Effects of smoking combined with intermittent hypoxia exposure on the lungs and vascular endothelial function in rats

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content