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新型抗重组磷脂酶 D1 IgG 完全中和了长尾蝎粗毒液的致死性。

Complete neutralization of the lethality of Hemiscorpius lepturus crude venom by a novel anti-recombinant phospholipase D1 IgGs.

机构信息

Venom and Biotherapeutics Molecules Lab., Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

出版信息

Toxicon. 2020 Aug;183:36-43. doi: 10.1016/j.toxicon.2020.05.010. Epub 2020 May 21.

DOI:10.1016/j.toxicon.2020.05.010
PMID:32445840
Abstract

Treatment of scorpion envenomation is a challenging issue since serotherapy is implemented by administration of polyvalent equine antisera. In our previous study we discovered that recombinant phospholipase D1 (Hl-RecPLD1) is responsible for the lethality of Hemiscorpius lepturus (H. lepturus) venom in mice. Accordingly, this study was aimed to investigate the protectivity of purified anti-Hl-RecPLD1 IgG against the lethality or major complications of H. lepturus venom. The neutralization efficiency of purified anti-Hl-RecPLD1 IgGs against sphingomyelinase activities of the crude venom and Hl-RecPLD1 was also assessed. Anti-Hl-RecPLD1 IgGs at optimum amount of 3.7 mg completely neutralized one Lethal Dose 100 (LD) of crude venom in mice. The anti-Hl-RecPLD1 IgGs remarkably reduced the necrosis area from 6.5 to 1 cm in rabbit derma, induced by the crude venom. The anti-Hl-RecPLD1 IgGs remarkably reduced the sphingomyelinase and hemolytic activities of crude venom as well. In conclusion, a novel rabbit monovalent IgG against Hl-RecPLD1 was able to completely protect the mice against the lethality of H. lepturus crude venom and reduced its toxicity as well. Such monovalent anti-Hl-RecPLD1 IgGs may have potential applications in serotherapy of H. lepturus envenomation.

摘要

蝎螫伤的治疗是一个具有挑战性的问题,因为抗血清疗法是通过给予多价马抗血清来实施的。在我们之前的研究中,我们发现重组磷脂酶 D1(Hl-RecPLD1)是 Hemiscorpius lepturus(H. lepturus)毒液在小鼠中致死的原因。因此,本研究旨在研究纯化的抗 Hl-RecPLD1 IgG 对 H. lepturus 毒液的致死性或主要并发症的保护作用。还评估了纯化的抗 Hl-RecPLD1 IgG 对粗毒液和 Hl-RecPLD1 的神经鞘磷脂酶活性的中和效率。最佳剂量为 3.7mg 的抗 Hl-RecPLD1 IgG 可完全中和小鼠中 1 个致死剂量 100(LD)的粗毒液。抗 Hl-RecPLD1 IgG 可显著减少粗毒液诱导的兔皮坏死面积,从 6.5 减少到 1cm。抗 Hl-RecPLD1 IgG 还显著降低了粗毒液的神经鞘磷脂酶和溶血活性。总之,针对 Hl-RecPLD1 的新型兔单价 IgG 能够完全保护小鼠免受 H. lepturus 粗毒液的致死性,并降低其毒性。这种单价抗 Hl-RecPLD1 IgG 可能在 H. lepturus 螫伤的抗血清治疗中有潜在应用。

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