Therapeutic Effects Investigation Of Cyclosporine A Associated With Methylprednisolone Against Paraquat-induced Pulmonary Fibrosis

Objective: Approach the influence of early alone or combination medication with cyclosporin A and high-dose methylprednisolone to lung tissue pathological change, oxidation-antioxidant targets and pulmonary fibrosis specific indicators in paraquat-induced pulmonary fibrosis rats. Contrast the pathological change and biochemical indicator detection condition in rat lung tissue circa medicine intervention, decision the curative effect. Methods: Erect a paraquat-induced pulmonary fibrosis animal model first. Determined five administration levels by refer to the literature reports (paraquat/kg ): 20 mg/kg, 25 mg/kg, 30 mg/kg, 35 mg/kg, and 40 mg/kg. Elect 40 rats divid into 5 groups, Each group 8 rats, inject paraquat-solution one time to abdominal follow dosages above-mentioned. Observation the state of the rats after poisoned, calculate the mortality after two weeks. Execute the survival rats, get parts of the lung tissue to do HE dyeing to observation the patho-change condition, picrosiru-red dyeing to observation the content change of the collagen fibers typeⅠand typeⅢ. Determine the model-poisoned dose by means of the fibers and the mortality. Then, evolve the medicine intervention experiment base on modelling to succeed. 176 male Wistar rats are divided into 5 groups random, A: Normal control group, B: Model group, C: The Cyclosporine A group(C1, C2, C3 each 16), D: Methylprednisolone group ( D1, D2, D3 each 16), E: The Cyclosporine A and Methylprednisolone group(E1, E2, E3 each 16). Inject in belly cavity by paraquat -solution to B, C, D, E group'rats, Inject in belly cavity by partes aequales NS to A group'rats. After poisoned 2h, 24h, 72h, inject to the C, D, E group'rats adoption the cyclosporine A, the methylprednisolone, the cyclosporine A associated with the methylprednisolone carry on a treatment. After poisoned 7 days later, 14 days later, take 8 rats in each group to execute to take lung, a part of lung tissue do HE dyeing and picrosiru-red dyeing to observe pathologic and fibrosis changes, a part of lung tissue make homogenate to measure the oxidation-antioxidant targets SOD, MDA, and pulmonary fibrosis specific indicators HPY in the lung organization. Compare with each biochemical indicator after treatment, and make sure curative effects. Results: 1. In the lung tissue of the model group'rats after poisoned 14 days, HE dyeing patho-observation can see that lung tissue occurrence bulk fibroblast paraplasm displace alveolar space, alveoli pulmonis nearly disappearance, incrassate alveolar septum inter-desis pellet. Picrosiru-red dyeing patho-observation can see that interior lung parenchyma bulk slender collagen fibers (Ⅰ-type more ), most encircle in alveolar sac and alveolar wall surrounding, distribution large ambit, densities higher, some place even form conferted collagen fibers bolus. 2. Compared with the model group, the cyclosporine A and methylprednisolone applied earlier period solo or combination treat paraquat poisoned rats can lessen the fibroblast paraplasm and alveolar septum thickening and alveoli space deflate, alveoli pulmonis obviously more than model group, condition of lung damage obviously lessen than model group. Picrosiru-red dyeing can see that collagen fibers encircle in alveolar sac and alveolar wall surrounding lessen than model group, distribution deflate ambit, densities lesson, espeeciallyⅠ-type collagen fibers. Each cure group compared to the model group there is disparity extent abatement, compared to the model control group difference is small, pulmonary fibrosis effluence and development obviously abatement. The contents of HPY and MDA in lung tissue of treatment groups were decreased obviously, SOD content increased, compared with the model group were significantly different, the comparison between the treatment group also has some differences. Earlier period Drug combination can prevention and cure paraquat-induced oxidative damage and fibrosis in the late obviously. 2h and 24h medication better than medication within 72h illuminates that the sooner the better. Conclusion: Paraquat poisoning provoke lung tissue oxidative damage and fibrosis change, Early cyclosporine A combine high-dose methylprednisolone pulse therapy can reduce the paraquat–induced acute lung injury, can be effective in preventing the occurrence of pulmonary fibrosis or reduce the severity of pulmonary fibrosis.