慢性阻塞性肺疾病急性加重期大鼠血清中性粒细胞弹性蛋白酶与肺功能的相关性分析

Analysis of correlation between serum neutrophil elastase and pulmonary function in acute exacerbation of chronic obstructive pulmonary disease rat model

目的:探究慢性阻塞性肺疾病急性加重期(AECOPD)大鼠血清中性粒细胞弹性蛋白酶(NE)与肺功能的相关性。方法:将40只Wistar大鼠随机分为正常对照组和AECOPD组,每组20只,其中正常对照组不作处理,AECOPD组通过熏吸香烟及气管内注射内毒素的方式建立COPD模型,并予以鼻腔内注射金黄色葡萄球菌构建AECOPD大鼠模型,观察两组大鼠肺组织病理形态学变化及建模后0周、4周、8周、12周体重变化,比较两组大鼠血清NE水平及肺功能指标[吸气阻力(Ri)、最大通气量(MVV)、0.3 s用力呼吸容积(FEV0.3)/用力肺活量(FVC)及呼气峰流速(PEF)],并通过Pearson相关性分析法分析NE与肺功能的相关性。结果:正常对照组肺组织肺泡结构完整,排列整齐,气管和支气管黏膜纤毛完整无脱落,未见明显炎性细胞浸润;AECOPD组肺泡结构明显破坏,肺泡壁变薄,肺泡腔不规则扩大,周围可见炎性细胞浸润,气道黏膜上皮杯状细胞增生,管壁纤维组织增生,支气管上皮细胞坏死、脱落。在8周、12周时AECOPD组大鼠体重低于正常对照组(P<0.05)。AECOPD组血清NE水平与Ri均较正常对照组升高,MVV、FEV0.3/FVC、PEF均较正常对照组降低(P<0.01)。AECOPD大鼠血清NE与Ri呈正相关关系(r=0.530,P=0.003),与MVV(r=-0.456,P=0.011)、FEV0.3/FVC(r=-0.395,P=0.031)、PEF(r=-0.554,P=0.002)呈负相关关系。结论:AECOPD血清NE水平升高与AECOPD肺功能持续下降密切相关。

Objective:To explore the correlation between serum neutrophil elastase(NE) and pulmonary function in rats with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods:A total of 40Wistar rats were randomly divided into normal control group and AECOPD group(n=20 per group).Normal control group gave no treatments.COPD model was established by smoking cigarettes and intratracheal injection of endotoxin,and AECOPD rat model was established by intranasal injection of staphylococcus aureus in AECOPD group.The pathomorphological changes of lung tissue and the changes of body weight at 0,4,8 and 12 weeks after modeling were observed.The levels of serum NE and pulmonary function indexes such as inspiratory resistance(Ri),maximal ventilatory volume(MVV),0.3 second forced expiratory volume(FEV0.3)/forced vital capacity(FVC) and peak expiratory flow(PEF) were compared between the two groups,and the correlation between NE and pulmonary function was analyzed by Pearson analysis.Results:In the normal control group,the alveolar structure was intact and neatly arranged.The trachea and bronchial mucosal cilia were intact with no exfoliation,and there was no obvious inflammatory cell infiltration.In the AECOPD group,the alveolar structure was obviously destroyed,the alveolar wall became thinner,the alveolar cavity expanded irregularly.The surrounding inflammatory cell infiltration,airway epithelial goblet cell proliferation,proliferation of fibrous tissue,bronchial epithelial cell necrosis and exfoliation were observed.At 8 and 12 weeks,the body weight of rats in the AECOPD group was lower than that in the normal control group(P<0.05).The levels of serum NE and Ri in AECOPD group were higher than those in normal control group,while the levels of MVV,FEV0.3/FVC and PEF were lower than those in normal control group(P<0.01).The serum NE of rats with AECOPD was positively correlated with Ri(r=0.530,P=0.003) and negatively correlated with MVV(r=-0.456,P=0.011),FEV0.3/FVC(r=-0.395,P=0.031) and PEF(r=-0.554,P=0.002).Conclusion:The increase of serum NE level in AECOPD is closely related to the continuous decrease of pulmonary function in AECOPD.