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蛋白质组学与扁尾海蛇(多带海蛇)毒液的中和:来自中国大陆和台湾地区的标本的种内比较。

Proteomics and neutralization of Bungarus multicinctus (Many-banded Krait) venom: Intra-specific comparisons between specimens from China and Taiwan.

机构信息

Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2021 Sep;247:109063. doi: 10.1016/j.cbpc.2021.109063. Epub 2021 Apr 25.

Abstract

The Many-banded Krait (Bungarus multicinctus) is a medically important venomous snake in East Asia. This study investigated the venom proteomes of B. multicinctus from Guangdong, southern China (BM-China) and insular Taiwan (BM-Taiwan), and the neutralization activities of two antivenom products (produced separately in China and Taiwan) against the lethal effect of the venoms. The venom proteomes of both specimens contained similar toxin families, notwithstanding small variations in the subtypes and abundances of minor components. More than 90% of the total venom proteins belong to three-finger toxins (3FTx, including alpha-neurotoxins) and phospholipases A (PLA, including beta-bungarotoxins), supporting their key involvement in the pathophysiology of krait envenomation which manifests as pre- and post-synaptic neurotoxicity. The venoms exhibited potent neurotoxic and lethal effects with extremely low i.v. LD of 0.027 μg/g (Bm-China) and 0.087 μg/g (Bm-Taiwan), respectively, in mice. Bungarus multicinctus monovalent antivenom (BMMAV) produced in China and Neuro bivalent antivenom (NBAV) produced in Taiwan were immunoreactive toward both venoms and their toxin fractions. The antivenoms neutralized the venom lethality variably, with BMMAV being more efficacious than NBAV by approximately two-fold. Findings suggest that the monovalent antivenom has a higher potency presumably due to its species-specificity toward the krait venom.

摘要

多带扁尾海蛇(Bungarus multicinctus)是东亚地区一种具有重要医学意义的毒蛇。本研究对来自中国广东(BM-China)和台湾岛(BM-Taiwan)的多带扁尾海蛇毒液蛋白质组进行了研究,并评估了两种抗蛇毒血清产品(分别在中国和台湾生产)对毒液致死效应的中和活性。尽管两种标本的毒液蛋白质组中存在毒素家族的相似性,但在次要成分的亚型和丰度上存在微小差异。超过 90%的总毒液蛋白属于三指毒素(3FTx,包括α-神经毒素)和磷脂酶 A(PLA,包括β-邦加毒素),这表明它们在眼镜蛇科蛇毒中毒的病理生理学中起着关键作用,表现为突触前和突触后神经毒性。这两种毒液在小鼠中具有很强的神经毒性和致死作用,静脉注射 LD 分别为 0.027μg/g(Bm-China)和 0.087μg/g(Bm-Taiwan),非常低。在中国生产的多带扁尾海蛇单价抗蛇毒血清(BMMAV)和在台湾生产的神经二价抗蛇毒血清(NBAV)均对两种毒液及其毒素组分具有免疫反应性。抗蛇毒血清对毒液致死效应的中和作用不同,BMMAV 的效果比 NBAV 大约高出两倍。研究结果表明,单价抗蛇毒血清的效力更高,可能是因为其对海蛇毒液具有种特异性。

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