CAJ | 학술논문

目的建立一种慢性阻塞性肺疾病相关肺动脉高压(COPD-PAH)小鼠模型.方法模型组小鼠第1天和第14天鼻内滴注脂多糖(LPS),其余时间每天熏烟4h,上下午各2h,10支香烟/h,6 d/周,持续熏烟3个月.对照组小鼠不做任何干预.建模期间监测小鼠体质量变化.建模结束后,检测以下指标:肺功能和右心压力;小鼠支气管肺泡灌洗液中炎症细胞总数和细胞类型;用ELISA方法检测肺组织中细胞因子KC和黏蛋白Muc5ac的水平.并观察气道和肺组织病理改变.结果与对照组相比,模型组小鼠体质量和动态肺顺应性显著降低,吸气阻力、右心室平均压和右心室重量/体质量比等显著增加.模型小鼠支气管肺泡灌洗液中白细胞总数升高,以巨噬细胞为主,并伴随中性粒细胞明显增加.肺组织KC和Muc5ac蛋白均较对照组明显增多.肺组织切片PAS染色显示模型组杯状细胞增生.此外,在模型组小鼠肺切片中观察到炎症浸润,气管壁和肺小血管壁平滑肌增厚,气管基底层下胶原沉积,提示气管和肺血管重塑的发生.结论用这种熏烟结合气道内滴注LPS的方法可以在短期内建立COPD-PAH小鼠模型.
목적 건립일충만성조새성폐질병상관폐동맥고압(COPD-PAH)소서모형.방법 모형조소서제1천화제14천비내적주지다당(LPS),기여시간매천훈연4h,상하오각2h,10지향연/h,6 d/주,지속훈연3개월.대조조소서불주임하간예.건모기간감측소서체질량변화.건모결속후,검측이하지표:폐공능화우심압력;소서지기관폐포관세액중염증세포총수화세포류형;용ELISA방법검측폐조직중세포인자KC화점단백Muc5ac적수평.병관찰기도화폐조직병리개변.결과 여대조조상비,모형조소서체질량화동태폐순응성현저강저,흡기조력、우심실평균압화우심실중량/체질량비등현저증가.모형소서지기관폐포관세액중백세포총수승고,이거서세포위주,병반수중성립세포명현증가.폐조직KC화Muc5ac단백균교대조조명현증다.폐조직절편PAS염색현시모형조배상세포증생.차외,재모형조소서폐절편중관찰도염증침윤,기관벽화폐소혈관벽평활기증후,기관기저층하효원침적,제시기관화폐혈관중소적발생.결론 용저충훈연결합기도내적주LPS적방법가이재단기내건립COPD-PAH소서모형.
Objective To establish a COPD-PAH mouse model induced by cigarette smoking exposure plus airway LPS inhalation.Methods Model mice were given LPS by intranasal inhalation on day 1 and day 14.The cigarette smoking exposure was carried out by two hours per time,twice every day,and 6 days per week in a dose of 10 pieces of cigarettes per hour within three months.Control mice didn't receive any treatment.The mice body weights were monitored during the process.The model establishment was evaluated according the following parameters: the lung function and right heart pressure; the total and differential cell numbers in bronchial alveolar lavage fluid (BALF) ;the KC protein and mucin Muc5ac levels in lung by ELISA; and the pathological changes on lung tissue.Results Compared with the control mice,the body weights and dynamic lung compliance were significantly reduced,the RI,right ventricular average pressure,right ventricular weight/body weight ratio,the total cells in BALF in which major cells were macrophages with augmented neutrophils,and the levels of lung KC and Muc5ac protein were significantly increased in model mice.The histological staining showed that goblet cell hyperplasia,lung inflammation,the thickening of smooth muscle layer on bronchia and lung small vessel and subepithelial collagen deposition occurred in model mice,which indicated the ongoing lung remodeling.Conclusions COPD-PAH mouse mode was established by cigarette smoking exposure plus airway LPS inhalation.This model can be used to study the effects of bacterial infection on COPD-PAH progress.