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Experiment Research Of Fluvastatin And Retinoic Acid In Rats With Radiation-induced Lung Injury

Posted on:2004-03-21Degree:MasterType:Thesis
Country:ChinaCandidate:J F YeFull Text:PDF
GTID:2144360092491846Subject:Internal Medicine
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Objective and significance of the study Radiation-induced lung injury (radiation pneumonitis and radiation pulmonary fibrosis) is a lung injury which normal lung tissues were radiated,when radiotherapy was used in thoracic tumor, and bone marrow was treated before transplantation, and nucleus accidence happened in peace period and war period. Its mechanism was complex. There were no effective prevention and treatment methods at present. The aim of the study was observed about the effect of retinoic acid(RA) as well as fluvastatin(Flu) in radiation lung injury, to inquire into the means of prevention and treatment lung injury induced by thoracic radiation.Methods1. 150 SD rats were randomly divided into :normal control(C), radiated control(R), treated groups with fluvastatin (F), retinoic acid (W ), treated group with Fluvastatin together with retinoic acid (L), dexamethasone (D) .2. The rats of group R, F, W, L, D were radiated with x-rays at a dose of 20 Gy and 15 Gy thoracically after anesthesia. The field of radiation was 4.5cmx4.5cm,and the rate of dose were 3Gy.min-1 and 2Gy.min-1,and the distance was 1m. Seven days before radiation the rats in group F started to be treated with fluat a dose of 20 mg per day by garaging .RA was gastrogavaged at a dose of 20mg-kg-1.d-1 in group W in the second day after radiation. RA and Flu were gastrogavaged at a dose of 10 mg.kg-1.d-1 in group L. Dexamethasone was gastrogavaged at a dose of S-SSmg-kg-1.d-1 in group D and continued to the end of the experiment.3. A part of lung tissues were observed by HE staining, Masson staining, toluidine blue staining and transmission electron microscope on the day 5, 15, 30, 60 after radiation. The density of mesenchyma were measured by image-analyzing system.4. Laminin and Hyaluromic acid in blood serum were messured by radioimmunoassay.5. The effect of Flu on expression of TGF-pl were observed by immunohistochemistry. Expression of TGF-beta ImRNA were measured by staining. The result of immunohistochemistry and in situ hybridization were measured by. image-analyzing system.6. The contents of endothelin-1 in plasma were measured on the day 5, 15, 30, 60. The slide was stained by immunohistochemitry. The results of immunohistochemitry were measured by image-analyzing system.7. The activity of prolidase in blood serum were measured by radioimmunoassay on the day 5, 15, 30, 60. The content of hydroxyproline was measured.8. Expression of interleukin-8, interleukin-8 mRNA and interleukin-18, interleukin-18 mRNA was measured by immunohistochemistry staining and in situ hybridization. The results of immunohistochemistry and in situ hybridization were measured by image-analyzing system.Results1. Group R suffered from markedly pneumonia and pulmonary edema on the day 30, 60. The area of mesenchyma increased in group R on the day 15( p<0.05) ,and more significant on the day 30 and 60(p<0.01). Collagenous fiber increased since 15 day in bronchus surrounding,vessel surrounding and under pleurisy.lt was obvious on the day 60. The quantity of mast cells increased, and it decreased in group F in corresponding times(p<0.01).2. Transmission electron microscope showed that type II pneumonocytes and endothelial cells of capillary were injuried in group R on the day 60 and revived in group F, W, Lin the same times; Collagenous fiber in lung tissues proliferated in group R on the day 5,but decreased in group F, W, L. There were no edema in mesenchyma.3. Hyaluromic acid significantly increased on the day 60 (p<0.01). Laminin increased on the day 30, 60 (p<0.05) ,while it droped in group F.4. Expression of TGF-01 was high gradually in group R , but its expression was dim in group F. The expression of TGF-beta ImRNA was high in group R on the day 30,60(P<0.01),and it was dim in group L and group W on the day 30(P<0.05), and more obvious on the day 60(P<0.01).5. Endothelin-1 increa...
Keywords/Search Tags:radiation-induced lung injury, rats, hyaluromic acid, laminie, TGF-β, retinoic Acid, fluvastatin, endothelin-1, prolidase, hydroxyproline, interleukin-8, interleukin-18
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