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费氏矛头蝮蛇毒对小鼠造成的局部和血液学改变

Local and hematological alterations induced by Philodryas olfersii snake venom in mice.

作者信息

Oliveira Juliana S, Sant'Anna Luciana B, Oliveira Junior Manoel C, Souza Pamella R M, Andrade Souza Adilson S, Ribeiro Wellington, Vieira Rodolfo P, Hyslop Stephen, Cogo José C

机构信息

Laboratory of Histology and Regenerative Therapy, Institute of Research and Development (IP&D), Vale do Paraíba University (UNIVAP), Avenida Shishima Hifumi, 2911, Urbanova, 12244-000, São José dos Campos, SP, Brazil.

Laboratory of Histology and Regenerative Therapy, Institute of Research and Development (IP&D), Vale do Paraíba University (UNIVAP), Avenida Shishima Hifumi, 2911, Urbanova, 12244-000, São José dos Campos, SP, Brazil.

出版信息

Toxicon. 2017 Jun 15;132:9-17. doi: 10.1016/j.toxicon.2017.03.013. Epub 2017 Mar 24.

Abstract

Envenomation by the South American opisthoglyphous snake Philodryas olfersii causes local pain, edema, erythema and ecchymosis; systemic envenomation is rare. In this work, we examined the inflammatory activity of P. olfersii venom (10, 30 and 60 μg) in mouse gastrocnemius muscle 6 h after venom injection. Intramuscular injection of venom did not affect hematological parameters such as red cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration. The venom caused thrombocytopenia (at all three doses), leukopenia and lymphopenia (both at the two highest doses), as well as neutrophilia (30 μg), monocytosis (30 μg) and basophilia (10 μg). Of the cytokines that were screened [IL-1β, IL-6, IL-10, IL-13, IL-17, TNF-α, IFN-γ, MIP-2 and KC] and IGF-1, only IGF-1 showed a significant increase in its circulating concentration, seen with 60 μg of venom; there were no significant changes in the cytokines compared to control mice. Histological analysis revealed the presence of edema, an inflammatory infiltrate and progressive myonecrosis. Edema and myonecrosis were greatest with 60 μg of venom, while the inflammatory infiltrate was greatest with 10 μg of venom. All venom doses caused the migration of polymorphonuclear and mononuclear leukocytes into muscle, but with no significant dose-dependence in the response. These findings show that, at the doses tested, P. olfersii venom does not cause hematological alterations and has limited effect on circulating cytokine concentrations. These data also confirm that the principal effects of the venom in mice are local edema, inflammatory cell infiltration and myonecrosis.

摘要

南美后沟牙毒蛇奥氏斜鳞蛇(Philodryas olfersii)的毒液注入会导致局部疼痛、水肿、红斑和瘀斑;全身性中毒较为罕见。在本研究中,我们检测了奥氏斜鳞蛇毒液(10、30和60微克)在注射毒液6小时后对小鼠腓肠肌的炎症活性。肌肉注射毒液对红细胞计数、血红蛋白、血细胞比容、平均红细胞体积、平均红细胞血红蛋白和平均红细胞血红蛋白浓度等血液学参数没有影响。毒液导致血小板减少(所有三个剂量组)、白细胞减少和淋巴细胞减少(两个最高剂量组),以及中性粒细胞增多(30微克剂量组)、单核细胞增多(30微克剂量组)和嗜碱性粒细胞增多(10微克剂量组)。在所筛选的细胞因子 [IL-1β、IL-6、IL-10、IL-13、IL-17、TNF-α、IFN-γ、MIP-2和KC] 以及IGF-1中,只有IGF-1的循环浓度显著升高,在注射60微克毒液时可见;与对照小鼠相比,细胞因子没有显著变化。组织学分析显示存在水肿、炎症浸润和进行性肌坏死。水肿和肌坏死在注射60微克毒液时最为严重,而炎症浸润在注射10微克毒液时最为严重。所有毒液剂量均导致多形核白细胞和单核白细胞迁移至肌肉,但反应中没有明显的剂量依赖性。这些发现表明,在所测试的剂量下,奥氏斜鳞蛇毒液不会引起血液学改变,对循环细胞因子浓度的影响有限。这些数据还证实,该毒液对小鼠的主要作用是局部水肿、炎症细胞浸润和肌坏死。

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