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幼年、亚成年和成年罗素蝰蛇毒液样本的比较成分和功能毒液图谱:与实验兔肾脏病理生理学的相关性

Comparative compositional and functional venomic profiles among venom specimens from juvenile, subadult and adult Russell's viper ( ): correlation with renal pathophysiology in experimental rabbits.

作者信息

Chaiyabutr Narongsak, Chanhome Lawan, Vasaruchapong Taksa, Laoungbua Panithi, Khow Orawan, Rungsipipat Anudep, Reamtong Onrapak, Sitprija Visith

机构信息

Queen Saovabha Memorial Institute, The Thai Red Cross Society, Pathumwan, Bangkok, Thailand.

Center of Excellence for Companion Animal Cancer, Department of Veterinary Pathology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.

出版信息

J Venom Anim Toxins Incl Trop Dis. 2022 Apr 4;28:20210111. doi: 10.1590/1678-9199-JVATITD-2021-0111. eCollection 2022.

Abstract

BACKGROUND

Eastern Russell's viper () is one of the most medically significant snakes responsible for the development of acute renal failure. However, variation of the clinical picture and renal pathophysiology following bites by young and adult have not been elucidated.

METHODS

In this study, we analyzed the venomic profiles of at different maturation stages of juvenile, subadult and adult groups. The same pooled venom from each group was subjected to enzymatic, electrophoretic and proteomic analysis, including sublethal toxicity (0.1 mg/kg iv.) examined on bodily functions by comparing the venom compositional and functional profiles among venom specimens from juvenile, subadult and adult by correlating them with the renal pathophysiology in experimental rabbits.

RESULTS

The comparative studies revealed that juvenile venom possessed higher phospholipase A, metalloproteinase and serine proteinase levels, while subadult and adult venoms contained more L-amino acid oxidase, phosphodiesterase, the Kunitz-type serine protease inhibitor, disintegrin families and endothelial growth factor. An study revealed that the adult and subadult venoms caused persistent hypotension and bradycardia, while thrombocytopenia was a more characteristic effect of juvenile venom. All venom age groups showed significant reductions in renal hemodynamics and electrolyte excretions. The juvenile venom caused a higher tubulonephrosis lesion score than adult and subadult venoms.

CONCLUSIONS

The venom shows an ontogenetic shift in its compositions and activities. Renal function alterations after envenomation depend on either the synergistic actions of different venom components or the disproportionate expression between the concentrations of enzymatic and non-enzymatic proteins in each age venom group. The high proportion of enzymatic toxin proteins in the juvenile venom results in greater nephrotoxicity.

摘要

背景

东方罗素蝰蛇是导致急性肾衰竭的最具医学意义的蛇类之一。然而,幼蛇和成年蛇咬伤后的临床表现和肾脏病理生理学变化尚未阐明。

方法

在本研究中,我们分析了幼年、亚成年和成年组不同成熟阶段的东方罗素蝰蛇的毒液成分。对每组相同的混合毒液进行酶学、电泳和蛋白质组学分析,包括通过静脉注射0.1mg/kg的亚致死毒性,通过比较幼年、亚成年和成年东方罗素蝰蛇毒液标本的毒液成分和功能特征,并将它们与实验兔的肾脏病理生理学相关联,来检测其对身体功能的影响。

结果

比较研究表明,幼蛇毒液中磷脂酶A、金属蛋白酶和丝氨酸蛋白酶水平较高,而亚成年和成年蛇毒液中含有更多的L-氨基酸氧化酶、磷酸二酯酶、库尼茨型丝氨酸蛋白酶抑制剂、去整合素家族和内皮生长因子。一项研究表明,成年和亚成年蛇毒液会导致持续性低血压和心动过缓,而血小板减少是幼蛇毒液更具特征性的作用。所有毒液年龄组的肾脏血流动力学和电解质排泄均显著降低。幼蛇毒液导致的肾小管肾病病变评分高于成年和亚成年蛇毒液。

结论

东方罗素蝰蛇毒液在其成分和活性上表现出个体发育转变。中毒后的肾功能改变取决于不同毒液成分的协同作用,或每个年龄毒液组中酶蛋白和非酶蛋白浓度之间的不成比例表达。幼蛇毒液中酶毒素蛋白的高比例导致更大的肾毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70c3/8978910/ce42e1bb3367/1678-9199-jvatitd-28-e20210111-gf1.jpg

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