褪黑素对大鼠应激性溃疡的保护及胃粘膜核因子-κB活性的影响

Effects of melatonin on gastric lesions and mucosal nuclear factor-κB (NF-κB) activation in rats with stress ulcer

目的 :探讨褪黑素 (melatonin ,MT)对大鼠应激性溃疡的保护作用及对胃粘膜核因子 κB(NF κB)活化的影响 ,阐明MT的作用机制。方法 :采用浸水 -束缚 (WIR)应激实验复制大鼠应激性溃疡模型。应激前 30min ,MT 5、2 0mg·kg-1组和应激组大鼠分别腹腔注射MT 5、2 0mg·kg-1和等体积生理盐水。应激 6h后 ,观察各组大鼠胃粘膜病变清况 ,对溃疡指数 (UI)进行评分 ,同时检测各组大鼠胃粘膜内丙二醛 (MDA)含量和NF κB活化清况。结果 :WIR应激6h后 ,与应激组比较 ,MT 5、2 0mg·kg-1组大鼠胃粘膜病变明显减轻 ,UI显著降低 (P <0 .0 1) ,胃粘膜MDA水平和NF κB活性也显著下降 (P <0 .0 1)。MT 2 0mg·kg-1组大鼠UI(P <0 .0 5 )和胃粘膜MDA水平 (P <0 .0 1)均显著低于MT 5mg·kg-1组 ,但两组间胃粘膜NF κB活性无显著性差异 (P >0 .0 5 )。结论 :MT可有效预防应激性溃疡的发生 ,其机制可能与MT抑制氧化应激诱导的NF κB过度活化有关。

AIM: To investigate the effects of melatonin on gastric lesions and mucosal nuclear factor κB (NF κB) activation in rats with stress ulcer for elucidating the molecular mechanisms of melatonin intervention in vivo. METHODS: Stress ulcer was induced by water immersion restraint (WIR) stress for 6 h. Melatonin (5 and 20 mg·kg -1 , ip) was administrated 30 min before WIR stress. After 6 h of WIR, rats were killed and the stomachs were removed. Ulcer index (UI) was used for evaluated macroscopic injury and gastric mucosal MDA contents and NF κB activation were determined. RESULTS: Severe gastric lesions were induced after WIR stress for 6 h. There was a significantly increased in MDA contents (P< 0.01 ) and NF κB activation (P< 0.01 ) in gastric mucosal in stress group. The gastric lesions in MT 5 mg·kg -1 group and 20 mg·kg -1 group were significantly relieved than that in the stress group after 30 min administration of melatonin (P< 0.01 ). The UI (P< 0.05 ) and mucosal MDA contents (P< 0.01 ) in MT 20 mg·kg -1 group were significantly lower than that in MT 5 mg·kg -1 group. But there was no significantly difference in mucosal NF κB activity between two groups. CONCLUSION: Melatonin can prevent the development of stress ulcer via a mechanism involving in reducing oxidative stress induced NF κB activation in gastric mucosa.