Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.
Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China; Tianjin Key Laboratory of Chinese Medicine Pharmacology, Tianjin, 301617, China; State Key Laboratory of Component-based Chinese Medicine, Tianjin, 301617, China.
Eur J Pharmacol. 2024 Jan 5;962:176187. doi: 10.1016/j.ejphar.2023.176187. Epub 2023 Nov 19.
Renal ischemia-reperfusion (I/R) is one of the main causes of acute kidney injury (AKI), for which there is currently no effective treatment. Recently, the interaction between endoplasmic reticulum (ER) stress and pyroptosis during AKI has been investigated.
The purpose of this study was to investigate the protective effects of Gypenoside XVII (GP-17) against I/R-induced renal injury.
In this study, mice were divided into 6 groups, sham group, I/R group, GP-17 low-, medium-, high-dose group, and positive control 4-PBA group. The renal I/R was performed in mice by clamping the bilateral renal pedicles for 40 min, and then reperfusing for 24 h. Blood and kidney samples were collected for analysis.
The results showed that GP-17 improved renal function and alleviated renal histopathological abnormalities caused by I/R. In addition, GP-17 pretreatment significantly decreased the expression or phosphorylation of ER stress response proteins including BIP, p-PERK, and CHOP. Besides, GP-17 inhibited the expression of pyroptosis proteins including caspase-1, GSDMD, and apoptotic protein BAX. The inflammatory factor IL-1β in these GP-17 pretreatment groups was also significantly reduced.
GP-17 blocked NLRP3 inflammasome activation by inhibiting ERS, thereby inhibiting renal tubular cell pyroptosis and apoptosis, and prevented renal I/R injury.
肾缺血再灌注（I/R）是急性肾损伤（AKI）的主要原因之一，目前尚无有效的治疗方法。最近，AKI 期间内质网（ER）应激与细胞焦亡之间的相互作用受到了研究。
本研究旨在探讨绞股蓝皂苷 XVII（GP-17）对 I/R 诱导的肾损伤的保护作用。
本研究将小鼠分为 6 组，假手术组、I/R 组、GP-17 低、中、高剂量组和阳性对照 4-PBA 组。通过夹闭双侧肾蒂 40min 再灌注 24h 来建立小鼠肾 I/R 模型。收集血液和肾脏样本进行分析。
结果表明，GP-17 改善了肾功能并减轻了 I/R 引起的肾脏组织病理学异常。此外，GP-17 预处理显著降低了 ER 应激反应蛋白 BIP、p-PERK 和 CHOP 的表达或磷酸化。此外，GP-17 抑制了细胞焦亡蛋白包括 caspase-1、GSDMD 和促凋亡蛋白 BAX 的表达。这些经 GP-17 预处理组中的炎症因子 IL-1β 也显著减少。
GP-17 通过抑制 ERS 阻断 NLRP3 炎性小体的激活，从而抑制肾小管细胞焦亡和凋亡，防止肾 I/R 损伤。
