熏烟联合间歇低氧暴露对大鼠肺及血管内皮功能的影响  

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

作　　者：毕虹[1] 黄照明 和煦[1] 陈敏[1] 何剑 何乐伟 郭翔[1] 王丽艳[1] 杜俊毅[1] 周开华[1] 王清[1] 金志贤[1] 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)

机构地区：[1]昆明市第一人民医院甘美医院呼吸内科

出　　处：《中国呼吸与危重监护杂志》2019年第6期560-566,共7页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：国家自然科学基金(81560010);云南省应用基础研究计划项目(2017FE467[-100])

摘　　要：目的探讨熏烟联合间歇低氧双重暴露对大鼠肺和主动脉病理生理以及血管内皮损伤水平的影响。方法将24只6周龄SD大鼠随机分为4组,每组6只;对照组给予假熏烟暴露和正常氧暴露,熏烟暴露组予熏烟暴露,间歇低氧组予间歇低氧暴露,重叠组进行间歇低氧、熏烟双重暴露。8周后,测定大鼠体重、右心室肥厚指数(RVHI),评估肺组织、主动脉病理改变,检测血清中内皮素-1(ET-1)、内皮型一氧化氮合酶(e NOS)、血管内皮生长因子(VEGF)、基质细胞衍生因子-1(SDF-1α)的水平。结果熏烟暴露组、间歇低氧组、重叠组大鼠体重均较对照组轻,RVHI均较对照组高(均P<0.05);重叠组体重、RVHI与熏烟暴露组、间歇低氧组比较,差异有统计学意义(均P<0.05)。熏烟暴露组、间歇低氧组、重叠组血清中ET-1、VEGF、SDF-1α水平均较对照组高,eNOS水平较对照组低(均P<0.05),对照组、重叠组间差异最明显;肺组织、主动脉病理观察显示,熏烟暴露组、重叠组呈肺气肿改变,重叠组较熏烟暴露组更明显(均P<0.05);熏烟暴露组、间歇低氧组、重叠组均显示不同程度的肺间质炎症浸润、支气管壁淋巴细胞增生及肺纤维化,肺小动脉壁呈现不同程度增厚、纤维化、周围炎症浸润等改变;熏烟暴露组、间歇低氧组、重叠组呈现不同程度的主动脉内皮细胞损伤、中膜增厚、胶原纤维增生情况;重叠组病理学特征更明显。结论烟熏、间歇低氧均可导致大鼠不同程度的肺组织和血管内皮损伤、血管内皮保护性因子减少,导致血管内皮细胞功能紊乱,引起肺小动脉、主动脉发生增厚、纤维化等结构重塑。而烟熏联合间歇低氧双重暴露可导致病理损伤更严重。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.After8 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(e NOS),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-1αin 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 e NOS 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-expo

关 键 词：熏烟 肺气肿 间歇低氧 阻塞性 睡眠呼吸暂停 重叠 内皮 大鼠 

分 类 号：R73[医药卫生—肿瘤]