褪黑素对内毒素血症大鼠胸主动脉诱导型一氧化氮合酶活性的影响

Effect of Melatonin on Inducible Nitric Oxide Synthase Activity in Thoracic Aorta of Endotoxemia Rats

目的探讨诱导型一氧化氮合酶在褪黑素改善脂多糖诱导的体循环血管反应性失调中的作用。方法实验分为溶剂对照组、脂多糖组、脂多糖+褪黑素组和褪黑素组。制备离体胸主动脉环,应用血管张力检测技术检测各组血管环在诱导型一氧化氮合酶抑制剂氨基胍、或非特异性一氧化氮合酶抑制剂L-硝基精氨酸孵育前后对苯肾上腺素和乙酰胆碱的反应性变化;应用扫描电镜技术观察血管内皮超微形态学改变;酶法检测血管组织匀浆中诱导型一氧化氮合酶活性。结果褪黑素可显著改善脂多糖诱导的胸主动脉对缩血管剂苯肾上腺素的低反应性;氨基胍孵育后,脂多糖组和脂多糖+褪黑素组对苯肾上腺素的收缩反应分别提高了51.43%和24.53%,差异有显著性(P<0.01);与脂多糖组比较,脂多糖+褪黑素组的诱导型一氧化氮合酶活性显著降低(P<0.05)。结论褪黑素对诱导型一氧化氮合酶有一定的抑制作用,这可能是褪黑素改善内毒素血症大鼠的血管反应性失调的机制之一。

Aim To investigate the effect of melatonin（MT） on the activity of inducible nitric oxide synthase in thoracic aorta of endotoxemia rats.Methods Sprague-Dawley rats were divided into four groups randomly： Vehicle group,Lipopolysaccharide（LPS） group（LPS 4 μg/g）,LPS＋MT group（MT5 μg/g,i.p.） which was given in twice,one injected 30 min before LPS and the other injected 60 min after LPS（4 μg/g,i.p）,and MT group.Six hours after LPS injection,rats were killed and thoracic aortic rings were prepared.The contraction response to phenylephrine and the endothelium-dependent relaxation response to acetylcholine before and after the incubation of aminoguanidine and Nω-nitro-L-arginine（L-NNA） were observed with the isolated artery rings technique.Inducible nitric oxide synthase activity in the artery tissues were detected.The ultrestructure of endothelium on the artery was observed by scanning electron microscope.Results Compared with LPS group,thoracic aortic rings in LPS＋MT group exhibited an increased contraction response to phenylephrine.After incubation with aminoguanidine,the contractile response to phenylephrine increased significantly in LPS and LPS＋MT group.Inducible nitric oxide synthase activity in LPS＋MT group decreased markedly compared with that of LPS group in thoracic aorta.Conclusion The protective role of MT on vascular activity in endotoxemia may be due to its properties to inhibit inducible nitric oxide synthase in a certain degree.