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马来西亚金马伦高原腹蛇的毒液组学:毒液蛋白质组学、毒性和抗蛇毒血清中和作用的见解。

Venomics of , the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom.

机构信息

Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;.

Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.

出版信息

Toxins (Basel). 2019 Feb 6;11(2):95. doi: 10.3390/toxins11020095.

Abstract

is a montane pit viper that causes bites and envenomation to various communities in the central highland region of Malaysia, in particular Cameron's Highlands. To unravel the venom composition of this species, the venom proteins were digested by trypsin and subjected to nano-liquid chromatography-tandem mass spectrometry (LC-MS/MS) for proteomic profiling. Snake venom metalloproteinases (SVMP) dominated the venom proteome by 48.42% of total venom proteins, with a characteristic distribution of P-III: P-II classes in a ratio of 2:1, while P-I class was undetected. Snaclecs constituted the second most venomous protein family (19.43%), followed by snake venom serine proteases (SVSP, 14.27%), phospholipases A₂ (5.40%), disintegrins (5.26%) and minor proteins including cysteine-rich secretory proteins, L-amino acid oxidases, phosphodiesterases, 5'-nucleotidases. The venomic profile correlates with local (painful progressive edema) and systemic (hemorrhage, coagulopathy, thrombocytopenia) manifestation of envenoming. As specific antivenom is unavailable for , the hetero-specific Thai Green Pit viper Monovalent Antivenom (GPVAV) was examined for immunological cross-reactivity. GPVAV exhibited good immunoreactivity to venom and the antivenom effectively cross-neutralized the hemotoxic and lethal effects of (lethality neutralizing potency = 1.6 mg venom per mL antivenom). The findings supported GPVAV use in treating envenoming.

摘要

是一种栖息在山地的蝰蛇,会对马来西亚中高原地区的各个社区(尤其是金马仑高原)造成咬伤和中毒。为了揭示该物种的毒液成分,我们使用胰蛋白酶消化毒液蛋白,并通过纳升级液相色谱-串联质谱(LC-MS/MS)进行蛋白质组学分析。蛇毒金属蛋白酶(SVMP)占毒液蛋白质组的 48.42%,具有 P-III:P-II 类的特征分布比例为 2:1,而 P-I 类未被检测到。Snaclecs 是第二大毒液蛋白家族(19.43%),其次是蛇毒丝氨酸蛋白酶(SVSP,14.27%)、磷脂酶 A₂(5.40%)、整联蛋白(5.26%)和一些小分子量蛋白,包括富含半胱氨酸的分泌蛋白、L-氨基酸氧化酶、磷酸二酯酶、5'-核苷酸酶。该毒液图谱与局部(疼痛性进行性水肿)和全身(出血、凝血功能障碍、血小板减少)中毒表现相关。由于没有针对 的特效抗蛇毒血清,我们检查了同种异源的泰国绿矛头蝮单价抗蛇毒血清(GPVAV)的免疫交叉反应性。GPVAV 对 毒液表现出良好的免疫反应性,抗蛇毒血清能有效中和 的血液毒性和致死作用(致死毒性中和效力=1.6 毫克毒液/毫升抗蛇毒血清)。这些发现支持使用 GPVAV 治疗 中毒。

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