褪黑素对大鼠肠缺血/再灌注损伤保护作用的实验研究

Experimental study on the protective effects of melatonin on intestinal ischemia-reperfusion injury in rats

目的 观察褪黑素对大鼠肠缺血 /再灌注损伤的保护作用。方法 成年雄性SD大鼠 6 0只分为假手术组 (10只 )、缺血 /再灌注组 (10只 )、缺血 /再灌注 +溶媒组 (10只 )、缺血 /再灌注 +褪黑素 10mg/kg组 (15只 )、缺血 /再灌注 +褪黑素2 0mg/kg组 (15只 )。观察肠缺血 30min再灌注 6 0min后肠黏膜损伤程度 ,测定血中D -乳酸和内毒素水平 ,并测定小肠组织中丙二醛 (MDA)、一氧化氮 (NO)水平和诱生型一氧化氮合酶 (iNOS)活力。结果 运用褪黑素组肠黏膜损伤程度轻 ,MDA、NO、iNOS和D -乳酸、内毒素均低于缺血 /再灌注组和溶媒组 ,并呈剂量依赖效应。肠黏膜损伤程度与MDA、NO及D -乳酸呈正相关。结论 运用褪黑素对大鼠肠缺血 /再灌注损伤有保护作用 ,效应呈剂量依赖性。这种作用的部分原因可能是褪黑素抑制了NO的过度生成。

Objective The purpose of this study was to assess the protective effect of melatonin on intestinal ischemia-reperfusion (IIR)injury in rats.Methods IIR injury was induced by clamping the superior mesenteric artery in rats for 30 min,followed by release of the clamp(reperfusion).Melatonin(10 mg/kg,20 mg/kg)or vehicle(control 2% alcohol)was administered twice,5 min prior to reperfusion and 30 min after the reperfusion period.At 60 min after reperfusion,rats were decapitated.Serum samples were taken for histological examination or the determination of malondialdehyde(MDA),nitric oxide (NO),catalase(CAT)and inducible isoform of nitric oxide synthase(iNOS)activity.Plasma D-lactate and endotoxin concentrations were measured for the evaluation of intestinal permeability.Results Compared with the sham-operation group,D-lactate,endotoxin and MDA,NO,iNOS were significantly increased,while CAT was decreased in ischemia-reperfusion group.Compared with ischemia-reperfusion group and vehicle administered group,these changes were reverted to some degrees by treatment with melatonin in a dose-dependent manner.The histopathologic results were consistent with the biochemical markers.Conclusion Melatonin protects effectively intestine from ischemia-reperfusion injury,the reason may inhibit the production of nitric oxide,and this effect is exerted in a dose-dependent manner.