The NOD-like receptor family pyrin domain-containing (NLRP3) inflammasomes is centrally implicated in cisplatin (CP)-induced kidney injury. Autophagy is critical for inhibiting production of NLRP3 protein that effectively reduces the inflammatory response. Ginsenoside Rg3 (SY), an active component extracted from ginseng, is reported to protect against CP-induced nephrotoxicity. However, the mechanisms underlying renoprotection by SY have not been established to date. Our results indicate that SY attenuated CP-induced apoptosis and damage in vivo and in vitro, as evidenced by increased cell viability, decreased the proportion of late apoptotic cells, elevated mitochondrial membrane potential, and ameliorated histopathological damage of the kidney. SY ameliorated CP-induced human renal tubular (HK-2) cells and kidney injury through upregulation of LC3II/I and beclin-1, inhibition of p62, NLRP3, ASC, caspase-1, and interleukin-1β. However, blockade of autophagy by 3-methyladenine reversed the suppression of SY on NLRP3 inflammasome activation and the protection of SY on HK-2 cells. Our collective results support the utility of SY as a therapeutic agent that effectively protects against CP-induced kidney injury by activating the autophagy-mediated NLRP3 inhibition pathway.

中文翻译：

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人参皂甙 Rg3 通过抑制细胞凋亡和自噬抑制的 NLRP3 减轻顺铂诱导的肾损伤

含有 NOD 样受体家族 pyrin 结构域 (NLRP3) 的炎性体与顺铂 (CP) 诱导的肾损伤密切相关。自噬对于抑制有效降低炎症反应的 NLRP3 蛋白的产生至关重要。据报道，人参皂甙 Rg3 (SY) 是一种从人参中提取的活性成分，可防止 CP 引起的肾毒性。然而，迄今为止，SY 保护肾脏的机制尚未确定。我们的研究结果表明，SY 在体内和体外减弱了 CP 诱导的细胞凋亡和损伤，这可以通过增加细胞活力、降低晚期凋亡细胞的比例、提高线粒体膜电位和改善肾脏的组织病理学损伤来证明。SY 通过上调 LC3II/I 和 beclin-1、抑制 p62、NLRP3、ASC、caspase-1 和白细胞介素 1β 来改善 CP 诱导的人肾小管 (HK-2) 细胞和肾损伤。然而，3-甲基腺嘌呤对自噬的阻断逆转了 SY 对 NLRP3 炎性体激活的抑制和 SY 对 HK-2 细胞的保护。我们的集体结果支持 SY 作为一种治疗剂的效用，通过激活自噬介导的 NLRP3 抑制途径，有效地防止 CP 诱导的肾损伤。