【摘要】 目的探讨褪黑素(MT)对脂多糖(LPS)诱导的内毒素血症大鼠肺动脉血管反应性紊乱的作用及相关机制。方法雄性SD大鼠分组如下:①溶剂对照组;②LPS组;③LPS+MT组;④MT组。检测各组大鼠血清总抗氧化能力;制备离体肺动脉血管环,应用血管张力检测技术检测各组血管环在iNOS抑制剂氨基胍、非特异性NOS抑制剂L-硝基精氨酸和血红素加氧酶-1抑制剂锌原卟啉孵育前后对苯肾上腺素和乙酰胆碱的反应性变化;应用HE染色和扫描电镜技术观察血管及内皮超微形态学改变。结果 LPS+MT组血清总抗氧化能力虽仍低于对照组水平(P<0.01),但是与LPS组相比明显增高(P<0.01);HE和电镜观察结果显示MT可减轻内毒素诱导的肺动脉组织的形态学改变;MT可显著改善LPS诱导的肺动脉对内皮依赖性舒张剂的低反应性,氨基胍和锌原卟啉孵育后,LPS组舒张反应继续下降,LPS组和LPS+MT组对PE的收缩反应均增高。结论 MT可以逆转肺动脉内皮依赖性舒张反应受抑,并能减少血管组织的结构损伤。更多还原

【Abstract】 Objective To investigate the effect of melatonin(MT) on the morphologic changes and endothelium-dependent relaxation responses of pulmonary artery in endotoxemia rats.Methods Sprague-Dawley rats were divided into four groups randomly: ①Vehicle group;② LPS group: LPS 4 mg/kg,i.p.;③LPS+MT group: MT(5 mg/ml,i.p.) was given in twice,one injected 30 min before LPS and the other injected 60 min after LPS(4 mg/kg,i.p);④MT group: Six hours after LPS injection,the rats were killed and thoracic aortic rings were prepared.The contraction response to phenylephrine(PE) and the endothelium-dependent relaxation response to acetylcholine(ACh) before and after the incubation of inducible NO synthase inhibitor aminoguanidine,non-selective NO synthase inhibitor N3-nitro-L-arginine or heme oxygenase-1 inhibitor zinc protoporphyrin.Serum total antioxidant capacities were detected by using kits.The ultrastructure of endothelium on the artery was observed by scanning electron microscope.Results Total antioxidant capacities in LPS+MT group increased markedly compared with that of LPS group.Significant structural injury in LPS group and alleviated structural changes in LPS+MT group were observed by scanning electron microscope.Compared with LPS group,the endothelium-dependent relaxation response to Ach by pulmonary artery rings in LPS+MT group was improved significantly.After incubation with aminoguanidine or zinc protoporphyrin,relaxation responses of pulmonary artery was impaired in LPS group and the contractile response increased significantly in LPS and LPS+MT group.Conclusions MT could reverse the depression of endothelium-dependent relaxation responses and alleviate the structural changes of pulmonary artery in endotoxemia rats.更多还原