The Research Of Maidong In Ameliorating Radiation-induced Pulmonary Fibrosis In Mice C57BL/6

Objective The incidence of the thoracic malignant tumors increased year by year.Radiotherapy is one of the main and effective treatment techniques in modern thoracic oncology therapeutic strategies.Radiation-induced lung-injury including the acute pulmonary pneumonitis and chronic pulmonary fibrosis are the main complications of the carcinoma,which becomes the major obstacle in thoracic radiotherapy.Owing to the molecular mechanisms of radiation-induced pulmonary-fibrosis is not yet revealed,the current treatment method is glucocorticoid.Unfortunately,a number of side-effects were observed during the long term use of glucocorticoid.Nowadays,lots of traditional Chinese medicine play a crucial role in alleviate the side effects of chemo-radiotherapy.The main purpose of this study is to assess the effects of Maidong in ameliorating the radiation-induced pulmonary fibrosis and study the underlying mechanisms.Methods and Materials 75 C57 BL / 6 rats were randomly divided into five groups,(1)blank control group(BC)(n=15)(2)radiation only group(RO)(n=15)(3)Traditional Chinese medicine(TCM)group(Maidong)(n=15)(4)western combination medicine(WCM)group(glucocorticoid combined with antibiotic)(n=15)(5)western signal medicine group(WSM)(glucocorticoid combined with antibiotic)(n=15).All the rats accept the whole thoracic radiation of a does of 12 Gy to generate the rat model of pulmonary fibrosis except for the rats in the blank control group.Maidong was given 1 times per day to the rats of Traditional Chinese medicine group.Glucocorticoid and antibiotic were given 1 times per day to the mice of western combination medicine group and glucocorticoid was given 1 times per day to the mice of western combination medicine group by intragastric administration in the last 4 weeks.All the rats were sacrificed at 28 weeks after the completion of the thoracic radiation.The serum levels Interleukin-6(IL-6)and Transforming growth factor-?1(TGF-?1)expression were evaluating by Elisa.The superoxide dismutase(SOD)activity and Malondialdehyde(MDA)in the lung were aslo measured.The pneumonitis and fibrosis score were obtained from the H & E staining.The hydroxyproline(Hyp)contents of the pulmonary and lung tissue were detected.Matrix-Metallo-Proteinases(MMP-2)and Tissue-Inhibitors of metallo-proteases(TIMP-2)expression were evaluating using immunohistochemistry.Results 1,H&E staining: Lung tissue sections of the BC group with H&E staining were normal.Lung tissue sections of the RO group were moderate inflammation,markedly thickened alveolar walls,depositions of collagen and diffuse accumulation of lymphocytes.Lung tissue sections of the TCM,WCM,WSM group were thickened alveolar walls,slightly depositions of collagen and diffuse accumulation of inflammation cells and fibroblast.The degree of depositions of collagen were slightly decreased,however the degree among the TCM,WCM,WSM were not apparently differences.2,the index of pulmonary fibrosis: 1)The index of pulmonary fibrosis:(1)the The serum levels TGF-?1 in BC group were significantly lower than RO group(0.000),TCM group(P=0.017),WCM group(P=0.011)and WSM group(P=0.015).Compared with RO group,TCM group(P=0.046),WCM group(P=0.04)and WSM group(P=0.05)were significantly lower at 28 weeks after thoracic radiation.The serum levels among WCM group WSM group and TCM were not any statistics difference.2)The contents of Hyp in BC group were significantly lower than the RO group(0.000),TCM group(P=0.008),WCM group(P=0.008)and TSM group(P=).However the contents of Hyp didn't show any difference in BC group and WSM group(P=0.082).Compared with RO group,WCM group(P=0.04)and WSM group(P=0.008)were significantly lower at 28 weeks after thoracic radiation.However the Hyp contents didn't show any difference between RO group and TCM group(P=0.054).The contents of Hyp among WCM group WSM group and TCM were not any statistics difference.3)The SOD activity in the BC group were significantly lower than TCM group(P=0.001),the WCM group(P=0.001)and WSM group(P=0.000).However the contents of Hyp didn't show any difference in the BC group and RO group(P=0.794).Compared with the RO group,the WCM group(P=0.001)and WSM group(P=0.001)and TCM group(P=0.001)were very significantly lower at 28 weeks after thoracic radiation.The SOD activity among WCM group WSM group and TCM were not any statistics differences.4)The serum levels IL-6(P=0.765)and the expression of MDA(0.377)among the BC,RO,TCM,WCM and WSM were not any statistics differences.5)The contents of MMP-2 in the BC group were significantly lower than RO(P=0.024),TCM group(P=0.000),the WCM group(P=0.001)and WSM group(P=0.022).Compared with the RO group,the WCM group,WSM group and TCM group were not any statistics differencesCONCLUSION Maidiong and glucocorticoid have the effects in ameliorating radiation-induced pulmonary fibrosis according to the followed mechanisms:1)downgrade the contents of TGF-?1 and Hyp.2)upgrade the activity of SOD in the lung.However the effect between Maidong and glucocorticoid was not any statistics differences.