Vasodilator and hypotensive effects of the spider peptide Lycosin-I in vitro and in vivo
Vasodilator and hypotensive effects of the spider peptide Lycosin-I in vitro and in vivo
复制标题
蜘蛛肽 Lycosin-I 的体外和体内血管扩张和降血压作用
DOI：
10.1016/j.peptides.2017.12.011
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发表时间：
2018-01-01
期刊：
影响因子：
3
通讯作者：
Jiang, Liping
中科院分区：
文献类型：
--
作者：
Ma, Binbin;Xi, Zhouhuan;Jiang, Liping
Lycosin-I是从新加坡狼蛛（Lycosa singoriensis）的毒液中分离的蜘蛛肽，在生物体中具有抗菌和抗癌特性。然而，Lycosin-I的心血管作用尚未研究。在本研究中，我们首次研究了Lycosin-I的血管扩张和扩张作用及其可能的机制，以开发一种有希望的治疗高血压相关疾病的药物。对于体外实验，分离胸主动脉，并将其分为两组，内皮完整和内皮剥脱的主动脉环。石蒜素-I对苯肾上腺素预处理的内皮完整的主动脉环有明显的舒张作用（p < 0.05），但对去内皮的主动脉环无明显舒张作用（p > 0.05）。一氧化氮合酶（NOS）抑制剂L-NAME（p < 0.001）和一氧化氮（NO）敏感性可溶性鸟苷酸环化酶（sGC）选择性抑制剂ODQ（p < 0.05）分别显著减弱Lycosin-I的血管舒张作用。用Western blot和臭氧化学发光技术检测，Lycosin-I预培养的人脐静脉内皮细胞的内皮型一氧化氮合酶（eNOS）磷酸化水平和NO生成量均显著高于对照组（p < 0.001）。在体内实验中，插入动脉和静脉导管，记录麻醉的自发性高血压大鼠的平均动脉压（MAP）和给药。与对照组相比，Lycosin-I在给药后2分钟引起MAP短暂下降（p < 0.001）。因此，Lycosin-I可能通过内皮依赖性血管舒张作用发挥抗高血压作用，eNOS和NO敏感性sGC是其中的两个主要参与因素。
Lycosin-I, a spider peptide isolated from the venom of the spider Lycosa singoriensis, has anti-bacteria and anticancer properties in organisms. However, cardiovascular effects of Lycosin-I have not been studied. In this study, we investigated for the first time the vasodilator and hypotensive effects of Lycosin-I and the possible mechanisms, in order to develop a promising treatment for hypertension-related diseases. For in vitro experiments, thoracic aortas were isolated, and divided into two groups, endothelium-intact and endothelium-denuded aortic rings. Lycosin-I induced a remarkable dose-dependent relaxation in endothelium-intact aortic rings pre-treated with phenylephrine (p < 0.05), while it showed no obvious vasodilator effects in endothelium-denuded aortic rings (p > 0.05). The vasodilator effects of Lycosin-I were significantly weakened by a nitric oxide synthase (NOS) inhibitor, L-NAME (p < 0.001) and a selective inhibitor of nitric oxide (NO)-sensitive soluble guanylate cyclase (sGC), ODQ (p < 0.05), respectively. The levels of endothelial nitric oxide synthase (eNOS) phosphorylation and the NO production were significantly higher in human umbilical vascular endothelial cells precultured with Lycosin-I than the control (p < 0.001), determined via western blot analysis and ozone-chemiluminescence technology. For in vivo experiments, arterial and venous catheters were inserted for mean arterial pressure (MAP) recording and drug administration in anaesthetized spontaneously hypertensive rats. Lycosin-I caused a transient drop of MAP 2 min after the administration compared with the control (p < 0.001). In conclusion, Lycosin-I has the potential to be an anti-hypertensive drug by endothelium-dependent vasodilatation, in which eNOS and NO-sensitive sGC are two main involved factors.