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The Research of Melatonin on the Expression of P38MAPK in Bleomycin-induced Pulmonary Fibrosis of Rats

Author: ZuoXiaoQing
Tutor: ShaoRunXia
School: Zhengzhou University
Course: Internal Medicine
Keywords: Pulmonary fibrosis P38 mitogen -activated protein kinase Bleomycin Melatonin Fibronectin
CLC: R563.9
Type: Master's thesis
Year: 2011
Downloads: 27
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Abstract

Background and Purpose pulmonary fibrosis (pulmonary fibrosis) is the kind of lung disease caused by a variety of reasons, the current unsatisfactory treatment, deepen the study of the mechanisms of pulmonary fibrosis, and looking for new treatment strategies imminent. It has been confirmed that oxidative stress plays an important role in an animal model of pulmonary fibrosis induced by bleomycin (bleomycin, BLM) the the P38 mitogen original activated protein kinase (P38mitogen-activated protein kinase of P38MAPK) pathway can oxidative stress signals activate melatonin (melatonin, MT) has a powerful antioxidant effect, therefore, the design of the experimental observation MT BLM induced pulmonary fibrosis in rats P38MAPK expression found for the prevention and treatment of pulmonary fibrosis new methods. 45 materials and methods of healthy female SD rats were randomly divided into three groups, 15 in each group, respectively, for the model group, the intervention group and the control group. Model group and the intervention group were injected intratracheal intratracheal instillation of BLM (5mg/kg), the control group, the same volume of saline. Intervention group in the two days before the modeling intraperitoneal injection of melatonin (4 mg/kg.d-1), model group and the control group intraperitoneally injected with same volume of saline. Each group, respectively, after the modeling and the 7th, 14th, 28th day of random five rats were sacrificed. The left lung immediately put in cryovials stored at -80 ℃ for PCR method, the right lung in a 10% formaldehyde for HE staining, Masson triple staining and immunohistochemical method checks. HE staining and Masson staining understand alveolitis and pulmonary fibrosis in rat lung tissue expression detected by immunohistochemistry method the rat lungs P38MAPK and FN; semi-quantitative reverse transcription - polymerase chain (RT-PCR ) the force detected lung tissue P38MAPKmRNA expression levels. Results of the pathological examination results show: the part of the seven days of the alveolar space of the model group smaller or collapse lung interval was significantly wider, inflammatory cell infiltration, inflammatory changes; 14 days reduced inflammatory cells, a small amount of collagen deposition; 28 days of lungs large collagen deposition, interstitial fibrosis change significantly. Lung tissue P38MAPK (protein and mRNA) and FN (protein) expression less in the control group, the model group enhanced expression in seven days, 14 days significantly increased, reaching a peak 28 days compared with 14 days began to weaken; The rise in the intervention group at all time points were lower than the model group, but still stronger than the control group, the data difference was statistically significant (P lt; 0.05). The conclusion P38MAPK and FN are involved in the formation of pulmonary fibrosis. Melatonin early intervention may block a P38MAPK expression, thereby reducing FN expression and deposition, and thus slow down the development of pulmonary fibrosis. Melatonin powerful antioxidant effects it may become a new drug for treatment of pulmonary fibrosis.

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