褪黑素对大鼠内毒素性肺损伤保护作用的研究

STUDY OF PROTECTIVE EFFECT OF MELATONIN ON LUNG INJURY INDUCED BY LIPOPOLYSACCHARIDE IN RATS

目的探讨褪黑素(melatonin,MT)对急性肺损伤(acute lung injury,ALI)大鼠的保护作用及其可能机制。方法96只大鼠随机分为4组:对照组气管内滴注生理盐水;另外3组气管内滴注等量脂多糖(lipopolysaccharide,LPS),并分别腹腔注射溶媒(1%乙醇生理盐水)、地塞米松(dexamethasone,DEX)和MT。各组分别于滴注试剂后3 h、6 h和12 h将动物处死,检测血清还原型谷胱甘肽(reduced glutathione,GSH)含量、肺组织超氧化物歧化酶(superoxide dismutase,SOD)活性及丙二醛(malonaldehyde,MDA)含量的改变,此外观察肺组织形态学变化。结果气管内滴注LPS使血清GSH含量及肺组织SOD活性较对照组明显降低(P<0.01),而MDA含量则显著升高(P<0.01),并且大鼠肺组织出现了明显的炎症性改变;MT处理组与LPS组比较,GSH含量和SOD活性显著升高(P<0.05或<0.01),而MDA含量明显下降(P<0.05或<0.01),同时肺组织的炎症改变也显著减轻。结论MT对ALI时的肺脏起明显的保护作用,其机制可能与MT清除过量的自由基有关。

Objective To investigate the protective effect of melatonin（MT） on acute lung injury（ALI） in rats and its possible mechanisms. Methods Ninety-six rats were randomly divided into four groups： normal saline （NS） was instilled intratracheally in control group; lipopolysaccharide（LPS） was instilled intratracheally in other three groups, then vehicle（1% alcohol in saline） .dexamethasone（DEX） and MT were injected intraperitoneally in these groups, respectively. All rats in each group were sacrificed at 3 h.6 h and 12 h after agent instillation. Reduced glutathione （GSH） content of serum, superoxide dismutase （SOD） activity and malonaldehyde （MDA） content of lung tissues were determined at different time points. In addition, morphological changes of lung tissues were also observed. Results Compared with control group, GSH content of serum and SOD activity of lung tissues decreased significantly after LPS administration（ P 〈0. 01）, but MDA content of lung tissues increased obviously（ P〈0.01）. In addition, LPS administration could also lead to severe inflammatory changes in lung tissues of rats. Compared with LPS group, MT treatment could mitigate inflammatory reaction in lung tissues, SOD activity and GSH content increased obviously（ P〈0.05 or 〈0.01） ,but MDA content decreased significantly （P〈 0.05 or 〈0.01）. Conclusion MT possessed obvious protective effect on lung tissues during ALI through scavenging excess free radicals.