| Chronic obstructive pulmonary diseases (COPD) is the most common disease of respiratory system which very difficult to cure. Pulmonary emphysema is a common disease severely threatening human health in worldwide. There is no effective drug to prevent the progressive loss of lung parenchyma at present. The destory 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 mechanism of forming 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 structural 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. Study on the treatment effect of giving all-trans retinoid acid on emphysema model in rats in different time periods and its intervention mechanism.Objective:.1.To build the emphysema model in SD rat with papain.2.Observe the morphological changes of lung tissues and the expression of protein of VEGF,VEGFR-2 and MMP-1,and BALF inflammatory cells. Study the effect of all-trans retinoid acid administration on emphysema model in rats in different time periods and its intervention mechanism.Methods: Male Sprague-Dawley (SD)rats(weighs about 180 to 220 grams) were randomly divided into 6 groups, normal saline control group (N), model group(P),early intervention group(R1),the mid-intervention group(R2),the late intervention group (R3),Cottonseed oil group(C).We constructed the rat model of emphysema by a single intratracheal instillation of 5% papain 1mL?kg-1 to the rats. Group N were given 1mL?kg-1 drip salt water. Given to groups R1 R2 R3 at different times by intraperitoneal injection of all-trans retinoic acid 500μg?kg-1, cottonseed oil group were given intraperitoneal injection of cottonseed oil. N and P groups were infused with normal saline and papain respectively,and then were feeded 60 days. Observe the morphological changes of lung tissues and the expression of protein of VEGF,VEGFR-2 and MMP-1,and BALF inflammatory cells.Results: For group R1 R2 R3 C and P,the morphometry analylyses indicated that NA decreased while mean alveolar area and mean line intercept increased comparing with group N. For group R1 R2 R3,the number of alveolar increased, mean alveolar area decreased comparing with group P and group C. Group R1 comparing with group R2 R3, the number of alveolar increased, mean alveolar area decreased.The expression of VEGF, VEGFR-2 were significangtly decreased in group P comparing with group N,while MMP-1 increased. The expression of VEGF, VEGFR-2 were significangtly increased in group R1 R2 R3 comparing with group P and group C,while MMP-1 decreased .There were no diference between the treatment groups .For group P, the total number of BALF cells, significantly higher than the group N, with macrophages and neutrophils mainly.Comparing with group C and group P the total number of BALF cells group of R1 R2 and R3 decreased,but there were no diference between the three treatment groups.Conclusion:1. Intratracheal instillation of papain can successfully replicate rat model of obstructive pulmonary emphysema. 2. The treatment of ATRA significantly promote alveolar morphology in rat ,might significantly promote alveolar repair .Cottonseed oil as a solvent, no therapeutic effect of emphysema. All-trans retinoid acid promote alveolar regeneration which may through regulating VEGF VEGFR-2,MMP-1. Early intervention is best.
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