| PrefaceEmphysema is a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by destruction of their walls and without obvious fibrosis. Proteinase - Antiproteinase imbalance is a primary inducement which leads to elastin and alveolar structure destruction. Recently many evidences suggest that there is daedal extracelluar matrix remodeling in the development of emphysema. Increased extracelluar matrix collagen deposition and abnormal collagen remodeling are a novel viewpoint in the pathogenesis of emphysema. The imbalance of MMPS/TIMPS secretion and the lose control of their activation play an important role in the process.So far,there is no available drug therapy to control COPD. Recently studies find that retinoic acid ( RA) can decrease the expression of collagenase, promote impaired epithelium reparation and increase elastin synthesis, which suggest that RA is beneficial to control COPD. Emphysema is related to elastase, so our study made emphysema models by intratracheal instillation elastase and use RA to prevent it, our aims are to study the express of metalloproteinase - 9 ( MMP - 9) and its tissue inhibitor - 1 ( TIMP - 1) in the lung of elastase - induced emphysema in rats and evaluate the effect andmechanism of retinoic acid ( RA) in preventing elastase - induced emphysema in rats in order to supply evidence to control human COPD.MaterialAnimal : Wistar rats, male, weight: 250 ?20 g Drugs ; elastase, Retinoic acid, lidocain , ketamine Reagent; MMP -9^TIMP - 1 Histostain TM - Plus Kits, SP Kit Instruments: analysis balance, light microscope, computer imaging analysis system, Olympus microphotographic system.Methods1. Experimental groups and preparation of emphysema model and treatment with retinoic acidTwenty - one male Wistar rats were randomly divided into three groups, the normal control group, the model group and the RA group , seven rats in each group. The rats were weighted 230 ~ 270 at the beginning of the test. The model group and the RA group were established by intratracheal instillation elastase (2.0 units/g body mass). The rats of the normal control group received an equal volume of saline, and the RA group was treated with RA (500ug/kg body mass) intraperitoneally on the first day of the study. Twenty - five days later, all rats were killed.2. Fixation, tissue sampling, and tissue preparationTwenty - five days later, rats were anesthetized with ketamine (60mg/kg) and killed by cutting the abdominal aorta. 10% Formalin( pH 7.4) was infused into the trachea at a transpulmonary pressure of 20 cm H2O. The trachea was ligated, lungs were removed from the thorax, and fixation was continued for 24 h -48h. The tissue specimens were sampled in the biggest distance of the lower left lung in rats and embedded in paraffin and sectioned into Sum thick slices. Then the tissue sections were stained with Haematoxylin - coin. The pathological changes were observed by light microscope, mean alveolar number ( MAN), mean alveolar area (MAA),mean linear intercept ( MLI) and parenchyma area/total area ( PA/TA) were measured by computer imaging analysis system, the expression of MMP - 9 and TIMP - 1 in the lung tissue were verified by immunohistochemical a-nalysis and image quantitative analysis.3. Statistical methodsValues were expressed as means ?s, Two - tailed unpaired t -test were used to analyze the data. A value of P <0. 05 was considered as the level of significance.Results1. Histopathological featuresObserved in the gross, the volume of lungs in emphysema model group were bigger than those in normal control group and RA group, color of lungs became paleness, elasticity of lungs lowered, and there were many alveolar combined into big ones in model group. Observed under the light microscope, alveolar tube and alveolar in the HE stained section of emphysema model group were obviously expanded, the walls of alveolar became thin and were broken. The brokeness of alveolar wal...
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