Establishment And Evaluation Of Rat Models With Chronic Obstructive Pulmonary Disease And Ventilator Induced Lung Injury

Chronic obstructive pulmonary disease(COPD) is a severe and life-threatening disease, which is characterized commonly by airway remodeling by hyperplasy of fibrous connective tissue and smooth muscle and air current blockage.The hazards of conventional mechanical ventilation are demonstrated by a number of recent studies that all show reduced mortality using improved ventilation strategies. The side effects of mechanical ventilation have been attributed to ventilator induced lung injury (VILI) and resulted pathological and functional injury. The isolated effects of primary lung injury and superimposed VILI can be difficult to separate, as the hallmarks of both include generalized inflammation, diffuse alveolar damage, and exudative edema. An inclusive understanding of the events responsible for VILI remains elusive.Establishment of animal models with ventilator induced lung injury and chronic obstructive pulmonary disease is of significance to pathogenesis, diagnosis and treatment. However, there are little literatures referring to the related models. Rats are one of the representational species with similar genes of humans, which is the suitable and controllable animal of experiments. Thus, establishment of ventilator induced lung injury and chronic obstructive pulmonary disease models in rats are very important to research of pathogenesis, diagnosis and treatment. There are two general approaches to model preparation, and further evaluation on lung function and pathological changes of lung tissues in rats with VILI and COPD. The overall study contains three contents:1. Establishment and evaluation on rat models with chronic obstructive pulmonary diseaseCOPD rat mode1s were established via cigarette inhalation (single group),cigarette inhalation and intratracheal LPS exposure( combined group) ,then pathomorphology of mode1s'lung and bronchia were investigated by HE staining and semiquantitative imagine analytic process.Result:The changes of pathology and lung function of this COPD rat model is as same as the changes of COPD patients; airway chronic inflammation, remodeling, air current blockage of combined group is worse than that of single group(P<0.01); tubal wall and smooth muscle layer of COPD models were thicken than that of normal control (P<0.01) and combined group is more obvious than single group at 20-day(P<0.01), at 40-day and 60-day , only the tubal wall was thicken than that of single group(P<0.01).2. Evaluation on lung function and pathological changes of lung tissues in rats with COPDCOPD models were established via passive smoking method in rats and the rats were randomly divided into 4 groups according the smoking time:4 weeks (group 4w),6 weeks (group 6w),and 8 weeks (group 8w)and control group that did not receive passive-smoking. Lung function and pathological changes of tissues were measured.Results:Peak expiratory flow (PEF) and intra-airway pressure slope (IP-slope) were significantly higher in group 6w and group 8w than in control group (P<0.01). The rates of airflow-limitation were higher in group 8w(100%)and group 6w(75%) than in group 4w(0) (P<0.01).Phenomena of airway-tissue thickening,airway narrowness,emphysema,airway wall infiltration of inflammatory cells,caliciform cell metaplasia,airway-wall necrosis,and hyperplasy of fibrous connective tissue and smooth muscle were more obvious in group 8w than in control group (P<0.01).In group 6w,6 of 8 rats had emphysematous characteristics and airway stenosi.And the degrees of inflammatory cell infiltration,caliciform cell metaplasia,airway-wall necrosis,hyperplasy of fibrous connective tissue and smooth muscle in this group were also higher than those in group control(P