Constructing The SD Rat Models Of Chronic Obstructive Pulmonary Emphysema And Effects Of Treatment By All-Trans-Retinoic Acid

Introduction:Chronic obstructive pulmonary disease(COPD) is the most common disease of respiratory system which is very difficult to cure.Pulmonary emphysema is a common disease threatening human health severely in worldwide.There is no effective drug to prevent the progressive loss of lung parenchyma at present.The destroy of elastic fiber breaks alveoli attachment,enlarges airspace,decreases gas exchange surface area and damages the elastic recoil in lung,so it plays a main role in the progress of this disease. The significant problem in clinical studies is how to explain the pathophysiological mechanisms of pulmonary emphysema,and then find the useful methods to cure and prevent COPD,which is the aim for many scholars.All-trans retinoic acid(ATRA),the biologically active metabolite of vitamin A, plays an important role in lung development,mature and maintaining alveolar architectural stability.It induces alveolar formation and increase elastic recoil in adult rat lung with elastase-induced emphysema,so it is probably an effective drug for treatment of pulmonary emphysema,but the mechanism is unclear.Objectives:1.To build the emphysema model in SD rat with porcine pancreatic elastase(PPE). 2.To evaluate effects of the All-Trans-Retinoic Acid(ATRA) with different concentrations on alveolar repair and pulmonary function in emphysema rats. Methods:Male Sprague-Dawley(SD) rats(weight range,170 to 220 g) were randomly divided into the following six groups:a controls group(N,n=10),an emphysemas group(P, n=10),a low-dose ATRA treatment group(R₁,n=10),a middle-dose ATRA treatment group(R₂,n=10),a high-dose ATRA treatment group(R₃,n=10) and a cottonseed oil group(C,n=10).In addition to group N,we constructed the rat models of emphysema by a single intratrachcal instillation of porcine pancreatic elastase(PPE) to rats.After 76 days,The ATRA treatment groups and Cottonseed oil group were individually treated with ATRA(500μg/kg,1000μg/kg,2000μg/kg) and cottonseed oil,intraperitoneally daily for 2 weeks.All rats were killed at 90 days,the analysis of artery blood gas,lung volume and alveolar morphometry of rats were performed.Experimental results were compared among normal group,model group,cottonseeds oil and ATRA treatment groups.Results:1.For rats in group P,we find the structures of lungs were disordered and the histopathology of the lungs revealed severe alveolar air space enlargement and some of the alveolar walls were destructed.Comparing with group N,the blood gas analysis indicated as following:the value of PCO₂ was increasing,while the value of PO₂ and SaO₂ were both decreasing(P＜0.05),and the same time,the lung volume increased obviously(P＜0.01).The morphometry analylses illustrated that NA increased obviously while MAA and MLI both increased obviously(P＜0.01).2.For rats in group R₁ and R₂,the pathological changes of emphysema were less,and comparing with group P,the lung volume decreased(P＜0.05).The morphometry analylses indicated that NA increased(P＜0.05) while MAA and MLI decreased (P＜0.05);and the blood gas analysis illustrated there were no difference about PCO₂, PO₂ and SaO₂(P＞0.05).Comparing with the group N,for the group R₁ and R₂,the lung volume increased obviously(P＜0.01),and PaO₂ and SaO₂ were not changing(P＞0.05),while the value of PaCO₂ increased(P＜0.05).The morphometry analylses indicated that NA decreased (P＜0.05),while MAA and MLI increased obviously(P＜0.01).There was no obvious difference between group R₁ and R₂.3.For group R₃ and group C,the pathological changes of emphysema were obvious, and comparing with group N,the blood gas analysis illustrated that PCO₂ increased while PO₂ and SaO₂ decreased(P＜0.05).The lung volume increased obviously (P＜0.01).The morphometry analylses indicated that NA decreased obviously,while MAA and MLI increased obviously(P＜0.01).The values of the above groups were not obvious different with the group N(all P＞0.05).Conclusion:1.We constructed the rat models of emphysema by a single intratrachcal instillation of porcine pancreatic elastase(PPE) to rats.2.The Low-dose and the Middle-dose ATRA treatment might significantly promote alveolar repair and remedy pulmonary malfunction,but with little effects on artery blood gas analysis in emphysematous rats.However,no positive effect was observed for High-dose ATRA treatment group.3.As the solvent,cottonseed oil had no effect on the experimental results.