褪黑素抑制大鼠急性肺损伤时核转录因子-κB的表达

Inhibitory effect of melatonin on the expression of nuclear factor-κB during acute lung injury in rats

目的探讨褪黑素（MT）对大鼠急性肺损伤（ALI）时肺脏的保护作用及其可能机制。方法将96只SD大鼠随机分为4组：对照组、脂多糖（LPS）组、地塞米松（DEX）和MT组，每组24只。采用气道内滴注LPS制备ALI大鼠模型；DEX和MT干预采用腹腔注射。分别于给药后3、6和12h活杀各组大鼠取肺组织标本，检测肺组织中髓过氧化物酶（MPO）和超氧化物歧化酶（SOD）活性及丙二醛（MDA）含量；用免疫组化方法检测核转录因子-κB（NF-κB）在肺组织的表达。结果LPS组各时间点SOD活性较对照组明显降低（P〈0．05或P〈0．01），而MPO活性与MDA含量以及NF-κB的表达则显著升高（P〈0．05或P〈0．01）；应用MT及DEX均能显著缓解上述变化（P〈0．05或P〈0．01）；上述各指标以6h变化最为显著，分别达到峰值或谷底。结论MT对ALI时肺脏的保护作用可能与MT清除自由基及抑制NF-κB的激活有关。

Objective To investigate the protective effect of melatonin （MT） on lung tissue during acute lung injury （ALI） in rats and its possible mechanism. Methods Ninety-six Sprague-Dawley （SD） rats were randomly divided into four groups： control group, lipopolysaccharide （LPS） group, dexamethasone （DEX） and MT treatment group, with 24 rats in each group. Rat model of ALI was established by instilling LPS intratracheally, and DEX and MT were injected intraperitoneally. All rats in each group were sacrificed at 3, 6 and 12 hours after intratracheal instillation of LPS, and lung tissue samples were harvested. Myeloperoxidase （MPO） activity, superoxide dismutase （SOD） activity and malondialdehyde （MDA） contents in lung tissue samples were detected in each group. In addition, the expression of nuclear factor-κB （NF-κB） was assessed with immunohistochemistry staining in lung tissues. Results Compared with control group, SOD activity in LPS group decreased at different time points significantly （P〈0. 05 or P〈0. 01）, but MPO activity, MDA content and the expression of NF-κB increased obviously （P〈0.05 or P〈0.01） ; the administration of MT and DEX could mitigate above values significantly （P〈0. 05 or P〈0. 01）. The changes in above each indexes were most obvious at 6 hours, either reaching the peak or the trough, respectively. Conclusion MT possesses protective effect on lung tissues during ALI through scavenging free radicals and inhibiting the activition of NF-κB.