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Neurogenic mediators contribute to local edema induced by Micrurus lemniscatus venom
PLOS Neglected Tropical Diseases ( IF 3.8 ) Pub Date : 2017-11-21 , DOI: 10.1371/journal.pntd.0005874
Luciana Lyra Casais-e-Silva , Catarina Teixeira

Background/Aims

Micrurus is one of the four snake genera of medical importance in Brazil. Coral snakes have a broad geographic distribution from the southern United States to Argentina. Micrurine envenomation is characterized by neurotoxic symptoms leading to dyspnea and death. Moreover, various local manifestations, including edema formation, have been described in patients bitten by different species of Micrurus. Thus, we investigated the ability of Micrurus lemniscatus venom (MLV) to induce local edema. We also explored mechanisms underlying this effect, focussing on participation of neuropeptides and mast cells.

Methodology/Principal findings

Intraplantar injection of MLV (1–10μg/paw) in rats caused dose- and time-dependent edema with a peak between 15 min and 1 h after injection. MLV also induced degranulation of peritoneal mast cells (MCs). MC depletion by compound 48/80 markedly reduced MLV-induced edema. Pre-treatment (30 min) of rats with either prometazine, a histamine H1 receptor antagonist or methysergide, a nonselective 5-HT receptor antagonist, reduced MLV-induced edema. However, neither thioperamide, a histamine H3/H4 receptor antagonist, nor co-injection of MLV with HOE-140, a BK2 receptor antagonist, altered the response. Depletion of neuropeptides by capsaicin or treatment of animals with NK1- and NK2-receptor antagonists (SR 140333 and SR 48968, respectively) markedly reduced MLV-induced edema.

Conclusions/Significance

In conclusion, MLV induces paw edema in rats by mechanisms involving activation of mast cells and substance P-releasing sensory C-fibers. Tachykinins NKA and NKB, histamine, and serotonin are major mediators of the MLV-induced edematogenic response. Targeting mast cell- and sensory C-fiber-derived mediators should be considered as potential therapeutic approaches to interrupt development of local edema induced by Micrurus venoms.



中文翻译:

神经源性介质促成蓝线虫毒液诱导的局部水肿

背景/目标

微型是巴西具有医学重要性的四个蛇类之一。从美国南部到阿根廷,珊瑚蛇的地理分布范围很广。尿液浓缩的特征在于导致呼吸困难和死亡的神经毒性症状。而且,在被不同种类的微粘虫咬伤的患者中,已经描述了包括水肿形成在内的各种局部表现。因此,我们研究了蓝线猴毒液(MLV)诱导局部水肿的能力。我们还探讨了这种作用的潜在机制,重点是神经肽和肥大细胞的参与。

方法/主要发现

大鼠足底内注射MLV(1–10μg / paw)引起剂量和时间依赖性水肿,注射后15 min至1 h达到峰值。MLV还诱导腹膜肥大细胞(MCs)脱粒。化合物48/80引起的MC耗竭显着降低了MLV引起的水肿。用异丙嗪,组胺H1受体拮抗剂或美塞麦肽(一种非选择性5-HT受体拮抗剂)对大鼠进行预处理(30分钟),可减轻MLV引起的水肿。但是,硫代过酰胺(一种组胺H 3 / H 4受体拮抗剂)和MLV与HOE-140(一种BK 2受体拮抗剂)的共同注射均未改变反应。辣椒素消耗神经肽或用NK 1-和NK 2治疗动物。受体拮抗剂(分别为SR 140333和SR 48968)显着减少了MLV引起的水肿。

结论/意义

总之,MLV通过激活肥大细胞和释放P物质的感觉C纤维的机制诱导大鼠爪水肿。速激肽NKA和NKB,组胺和5-羟色胺是MLV引起的水肿反应的主要介质。靶向肥大细胞和感官C纤维衍生的介体应被认为是中断由弥漫性毒液诱导的局部水肿发展的潜在治疗方法。

更新日期:2017-11-22
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