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肌肉注射矛头蝮蛇毒液会引发急性肾损伤(AKI):这是由于肾功能滤过受损、钠处理功能障碍和组织损伤所致。

Intramuscular injection of Bothrops jararaca venom provoked acute kidney injury (AKI): Underpinned by impaired renal filtration, Na handling, and tissue damage.

机构信息

Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde - Rio de Janeiro, RJ, Brazil.

Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Rio de Janeiro, RJ, Brazil.

出版信息

Toxicon. 2024 Nov 28;251:108159. doi: 10.1016/j.toxicon.2024.108159. Epub 2024 Nov 1.

DOI:10.1016/j.toxicon.2024.108159
PMID:39489350
Abstract

Globally, about 2.5 million people are victims of snakebites annually. In Brazil, the most clinically relevant snake is the Bothrops jararaca. The symptoms of envenomation are acute inflammation at the bite site and bleeding disorders. Despite kidney failure being the main cause of death after envenomation, kidney damage is not completely understood, and there are no clinically representative in vivo models. This work aimed to characterize the acute kidney injury (AKI) induced by intramuscular injection (IM) of Bothrops jararaca (Bjc) venom in male Wistar rats. The control group received 0.9% saline solution. Three doses of venom (3.5, 6.0, and 8.0 mg/kg) were administered IM into the posterior region of the right knee. After the injection, the rats were kept in metabolic cages. The following parameters were analyzed after 24 h: the extent of muscle damage and kidney damage (urinary creatinine, proteinuria, plasma creatinine, and renal tissue histology). All rats presented a hemorrhagic lesion at the injection site in a dose-dependent manner. Biochemical parameters indicated kidney damage: plasma creatinine accumulation, decreased glomerular filtration rate, albuminuria and proteinuria, and disturbance in Na homeostasis. Histological analyses showed glomerular injury, tissue discontinuity more evident in the cortex and tubular dilatation, and collagen deposition. The decline in renal function and tissue damage indicated the occurrence of AKI. Therefore, a Bjc venom-induced in vivo model of renal injury has been established for future studies.

摘要

全球范围内,每年约有 250 万人遭受蛇咬伤。在巴西,最具临床相关性的蛇是矛头蝮(Bothrops jararaca)。蛇咬伤的症状为咬伤部位急性炎症和出血性疾病。尽管肾衰竭是蛇咬伤后的主要死亡原因,但对肾脏损伤还不完全了解,也没有具有临床代表性的体内模型。本研究旨在描述雄性 Wistar 大鼠肌肉注射(IM)矛头蝮(Bjc)毒液引起的急性肾损伤(AKI)。对照组接受 0.9%生理盐水。将 3 种剂量的毒液(3.5、6.0 和 8.0 mg/kg)IM 到右膝后侧。注射后,大鼠被放入代谢笼中。24 小时后分析以下参数:肌肉损伤和肾脏损伤的程度(尿肌酐、蛋白尿、血浆肌酐和肾组织学)。所有大鼠均以剂量依赖性方式在注射部位出现出血性病变。生化参数表明存在肾脏损伤:血浆肌酐蓄积、肾小球滤过率降低、白蛋白尿和蛋白尿以及 Na 平衡紊乱。组织学分析显示肾小球损伤、组织连续性中断更明显的皮质和肾小管扩张以及胶原沉积。肾功能和组织损伤的下降表明 AKI 的发生。因此,已经建立了 Bjc 毒液诱导的肾损伤体内模型,用于未来的研究。

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