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磷脂酶 A 抑制剂瓦瑞昔布可预防黄蜂蜇伤诱导的大鼠肾毒性。

Phospholipase A inhibitor varespladib prevents wasp sting-induced nephrotoxicity in rats.

机构信息

School of Medicine, Wuhan University of Science and Technology, Wuhan, 430065, China; Department of Nephrology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441000, China.

Department of Nephrology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441000, China.

出版信息

Toxicon. 2022 Aug;215:69-76. doi: 10.1016/j.toxicon.2022.06.007. Epub 2022 Jun 17.

Abstract

This study aimed to clarify whether varespladib, a phospholipase A (PLA) inhibitor, can be used as a therapeutic agent for wasp sting-induced acute kidney injury (AKI). Rats were divided into control, AKI, and AKI + varespladib groups. The AKI model was established by subcutaneously injecting wasp venom at five different sites in rats. Varespladib treatment showed a significant inhibitory effect on wasp venom PLAin vitro and in vivo. Moreover, we observed that varespladib decreased the levels of rhabdomyolysis and hemolysis markers compared with that in the AKI group. Histopathological changes in the kidney decreased significantly, and rat serum creatinine levels were reduced after varespladib administration. The significantly regulated genes in the kidney of the AKI group were mostly involved in inflammatory response pathway, and the administration of varespladib remarkably attenuated the expression of these genes. Therefore, varespladib inhibited wasp sting-induced functional and pathological damage to the kidneys. We propose that the PLA inhibitor varespladib protects the kidney tissue in a wasp sting-induced AKI model by inhibiting PLA activity.

摘要

本研究旨在阐明磷脂酶 A(PLA)抑制剂伐瑞昔布是否可用于治疗黄蜂蜇伤引起的急性肾损伤(AKI)。将大鼠分为对照组、AKI 组和 AKI+伐瑞昔布组。通过在大鼠五个不同部位皮下注射黄蜂毒液建立 AKI 模型。伐瑞昔布在体外和体内均对黄蜂毒液 PLA 表现出显著的抑制作用。此外,我们观察到伐瑞昔布降低了肌溶解和溶血标志物的水平,与 AKI 组相比。肾组织的组织病理学变化明显减轻,给予伐瑞昔布后大鼠血清肌酐水平降低。AKI 组肾脏中显著调节的基因主要参与炎症反应途径,而伐瑞昔布给药显著减弱了这些基因的表达。因此,伐瑞昔布抑制了黄蜂蜇伤引起的肾脏功能和病理损伤。我们提出,PLA 抑制剂伐瑞昔布通过抑制 PLA 活性来保护黄蜂蜇伤诱导的 AKI 模型中的肾脏组织。

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