褪黑素对实验性肺纤维化p38MAPK表达的影响

目的观察褪黑素对博来霉素致大鼠肺纤维化p38丝裂原活化蛋白激酶（p38MAPK）表达的影响,从而探讨其防治肺间质纤维化的机制。方法雌性SD大鼠45只随机分为3组,每组15只,分别为模型组,干预组及对照组。模型组和干预组均一次性气管内注入博来霉素（5mg/kg）,对照组气管注入同体积生理盐水。干预组于造模前2d腹腔注射褪黑素4mg/（kg.d）],而模型组和对照组给予同体积生理盐水。每组分别于7、14、28d各随机处死5只大鼠。采用HE染色和M asson染色了解肺泡炎和肺纤维化的情况,用免疫组织化学方法检测肺组织p38MAPK和FN蛋白的表达;RT-PCR方法检测肺组织p38MAPK的水平。结果成功建立肺纤维化模型。肺组织中p38MAPK（蛋白和mRNA）和FN（蛋白）在对照组表达较弱,模型组在7d表达增强,14d明显增强,28d较14d开始减弱,干预组各期上升幅度均低于模型组,但仍强于正常组（P〈0.05）。结论褪黑素可能通过抑制p38MAPK的表达而减少FN的分泌和沉积,延缓肺间质损害的进程。

Effect of Melatonin on Expression of p38 Mitogen-activated Protein Kinase in Bleomycin-induced Pulmonary Fibrosis of Rats

Objective To observe the effect of melatonin on the expression of p38 mitogen-activated protein kinase（p38 MAPK） in bleomycin-induced pulmonary fibrosis of r ats,so as to elucidate the preventing and curative mechanisms of melatonin to pulmonary fibrosis.Methods Forty-five female SD rats were randomly divided into three groups（n=15 in each group）,including control group,Model group（intratracheal injected with bleomycin） and melatonin-treated group（intratracheal injected with bleomycin and intraperitoneal injected with melatonin）.The animals were killed on the 7th,14th and 28th day separately,The pathological model was evaluated by HE and Masson dyeing method,Immunohistochemistry was employed to detect the expression of p38MAPK and FN protein in lung of all groups.The mRNA level of p38MAPK in lung was examined by RT-PCR.Results The pathological model was successfully established.From 7 d to 28 d,the expression of p38MAPK（protein and mRNA）and FN（protein） were increased in model group compared with that in melatonin-treated group,especially on the 14th day（P0.05）,while were reduced on the 28th day.Conclusion Melatonin can inhibit the expression of p38MAPK in lung,and therefore reduce the deposition of FN and delay the process of interstitial injury in the lung of pulmonary fibrosis of rats.