Establishment Of A Rabbit Model Of Smoke-induced Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable common disease characterized by persistent airflow limitation which shows progressive development, accompanied by the increase of chronic inflammatory reaction of airway and lungs to noxious particles or gases. Acute exacerbation and complications affect the overall severity of the disease. Because its sick population is large, the mortality rate is high and it has become a major public health problem worldwide. Domestic investigations show that80%to90%of male lung cancer patients are associated with smoking and many patients have20to50years’ smoking history. Cigarette smoking is a major risk factor for airway hyperresponsiveness and COPD. The majority of these patients are combined with chronic bronchitis or emphysema. These patients have airway secretions, increased irritability, in the implementation of general anesthesia endotracheal intubation or double lumen endobronchial intubation and mechanical ventilation process, especially a long time of single lung ventilation, what kind of stress reactions the body will appear and how the lung will further react to pathological change, are the issues to be resolved by the anesthesia workers. Establishing an ideal model of smoke-induced chronic obstructive pulmonary disease is the most important step.20Male New Zealand white rabbits were randomly divided into2groups with10in each group, normal control group and smoke-induced model group. Those rabbits in smoke-induced model group were in self-made smoke cage, which has two layers (the upper and lower levels) which can move wholly. The rabbits placed in the upper levels, at the lower levels alcohol lamps are placed to burn thin copper plate on smoking tobacco.15g pure cut tobacco was burned at a time. The rabbit cages were surrounded by homemade cloth, the upper walls were connected to a modification of the ventilation fans. Exposed to smoke for0.5hour once,2times per day, lasted for70days. Those rabbits in normal control group were not exposed to smoke. During the experimental process, the rabbits were observed carefully and weighed every week. All rabbits were anesthetized at no smoking for1week after the last smoke exposure, the arterial blood gases were analyzed and the pulmonary function was tested before being sacrificed. Protein content in right lung bronchoalveolar lavage fluid (BALF) was measured and leukocyte count and classification were also done. The removed left lung tissues were stained with hematoxy lin-eosin for histomorphology observation.The rabbits pulmonary function test and the rabbits lung tissue pathology can determine that the pathology change in COPD rabbits model conforms to the human COPD characteristic.(1)Smoke-induced rabbits’spirit is more sluggish, the action is not flexible enough, the weight grows slower, smoke-induced up to60days with1only limp to death.(2) Blood gas analysis results:The artery blood oxygen pressure and the artery blood oxygen saturation in smoke-induced model group [(81.3±6.4) mmHg,(96.7±1.4)%] is significantly lower compared with normal control group [(95.6±10.1) mmHg,(99.1±1.2)%], arterial partial pressure of carbon dioxide (44.2±5.3)mmHg increases than normal control group (36.1±4.8)mmHg, the difference has statistics significance(P<0.05); the power of hydrogen in smoke-induced model group(7.29±0.56) has no significant changes compared to normal control group(7.38±0.20), the difference was not statistically significant (P>0.05).(3) The results of rabbits pulmonary function shows:percentage of forced expiratory volume in first0.3second/Forced vital capacity(FEV0.3/FVC) and dynamic lung compliance(DLC) were significantly decreased in smoke-induced model group [(69.15±2.17)%,(0.89±0.18)ml·cmH2O-1] compared with normal control group [(91.48±6.26)%,(2.26±0.31)ml·cmH2O-1]; The expiratory resistance assay showed that the level was significantly increased in smoke-induced model group (39.31±1.83)cmH2O·1-1·s-1compared to normal control group (25.42±2.24)cmH2O·l-1·s-1, the difference has statistics significance (P<0.05).(4) Protein content, total white blood cell and neutral granular cell number in BALF were all significantly increased in smoke-induced model group[(335±69)mg·l-1,(150±37.0)×104·l-1,(63±4)%] compared with normal control group [(117±9.8)mg·l-1,(3.7±0.6)×104·l-1,(<1)%], the difference has statistics significance (P<0.05).(5)Macroscopic observation:smoke-induced model group rabbit’lung volume increases, visible uneven pale foci, poor elasticity, four cases of lung edge portion have been blackened. Histomorphology observation by light microscopy:bronchial lung tissue of smoke-induced model group ciliated columnar epithelial cells were partially exfoliation, cilia adhesion, inverse, degeneration, necrosis and some falling off significantly, a large number of inflammatory cell infiltration, bronchial smooth muscle thickening can be see in goblet cell hyperplasia, submucosal and muscle layers; The alveolar expansion of integration, significant thickening of the alveolar septa shows inflammatory cell infiltration and capillary dilatation and congestion.A smoke-induced chronic obstructive pulmonary disease rabbit model was established successfully, it conforms to the development pathology physiology condition of human COPD, and it should endure a long time one-lung ventilation after being anesthetized. It provides the basis of the experimental study for the study of smoking-induced COPD patients in the anesthesia process of double-lumen endobronchial intubation strong stimulation and a long time of single lung ventilation lung further damage in the pathogenesis, effective prevention and treatment of drug applications.