The Research Of Melatonin On The Expression Of P38MAPK In Bleomycin-induced Pulmonary Fibrosis Of Rats

Backgroud and ObjectivesPulmonary fibrosis is causeded by a lot of reasons,while clinical treatments are inefficacious.So further research of pathogenesis of pulmonary fibrosis and hunting for new therapies are urgent tasks.First of all,Literature have confirmed that oxidatice stress plaied an important role in bleomycin-induced pulmonary fibrosis. Secondly,Signal path of P38mitogen-activated protein kinase could be activated by oxidatice stress.Thirdly,melatonin can resist oxidatice stress.So the experiment aims to observe the effect of melatonin on the expression of P38 mitogen-activated protein kinase(P38MAPK) in bleomycin-induced pulmonary fibrosis of rats, so as to find the new therapy of pulmonary fibrosis.Materials and MethodsForty-five female healthy SD rats were randomly divided into three groups (n=15in each group)which included model group, melatonin-treated group and control group.Rats in model group and melatonin-treated group were injected with bleomycin in trachea(5mg/kg),while melatonin-treated group were given melatonin (4mg/kg.d-1)by intratracheal injecting two days before instilling bleomycin.Control group and model group were instilled with equal normal saline.Five rats of each group were killed on the 7th,14th and 28th day separately,50 percent of lung tissue sample was immediately preserved -80℃in order to observe the expression of P38MAPK mRNA by semi-quantitative RT-PCR.The rest of lung tissue sample was conserved in formaldehyde in order to use HE and Masson dyeing methods to measure the pathological model and employ immunohistochemistry to detect the levels of P38MAPK and FN protein of pulmonary tissue.ResultsThe pathological result showed that plentiful cells of inflammation assembled in the pulmonary tissue while pulmonary fibrosis was not serious on the 14th day and pulmonary fibrosis was extremely oibvious on the 28th day,which indicated that the pathological model was successfully established.From 7th day to 14th day,the expression of P38MAPK (protein and mRNA) and FN in model group were increased gradually and from 14th day to 28th day they decreased gradually,and it was higher than that in control group.The expression in melatonin-treated group decreased less visibly than that in model group,while increased more visibly than that in control group.The differences above were significant(P<0.05).ConclusionsBoth of P38MAPK and FN play an important role in the process of pulmonary fibrosis.Melatonin can inhibit the expression of P38MAPK in lung tissue,and therefore reduce the deposition of FN and delay the process of interstitial injury in the lung of pulmonary fibrosis of rats.The process was remarkably weaken by melatonin. Melatonin may become a potential drug to treat pulmonary fibrosis.