Sodium aescinate protects renal ischemia-reperfusion and pyroptosis through AKT/NLRP3 signaling pathway

Renal ischemia-reperfusion injury (RIRI) is a common cause of acute renal injury. Studies have shown that sodium aescinate (SA) may serve as a potential therapeutic agent, although its exact mechanism remains unclear. This study first evaluated the efficacy of SA using a mouse renal ischemia-reperfusion model. Subsequently, its mechanism was elucidated through systematic bioinformatics, and finally validated through <i>in vitro</i> and <i>in vivo</i> experiments. The results demonstrated that SA has a protective effect on renal function in mice with RIRI. Bioinformatic analysis indicated that the pyroptosis pathway is significantly activated during renal ischemia-reperfusion injury, and immunohistochemistry showed that the level of renal pyroptosis is upregulated during ischemia-reperfusion injury. Administration of SA was able to reduce the expression of pyroptosis-related proteins (GSDMD, NLRP3, IL-1β) in RIRI. <i>In vitro</i> and <i>in vivo</i> experiments further confirmed that SA exerts an anti-pyroptotic effect by inhibiting the AKT/NLRP3 signaling pathway. Ultimately, SA mitigates kidney injury in IRI mice by suppressing renal failure through inhibition of the AKT/NLRP3 signaling pathway.

肾缺血再灌注损伤（renal ischemia-reperfusion injury, RIRI）是急性肾损伤的常见致病原因。研究表明，七叶皂苷钠（sodium aescinate, SA）或可作为潜在治疗制剂，但其确切作用机制尚未阐明。本研究首先通过小鼠肾缺血再灌注模型评估了SA的治疗功效；随后借助系统生物信息学手段解析其作用机制，并最终通过体外（in vitro）与体内（in vivo）实验完成验证。结果显示，SA对肾缺血再灌注损伤模型小鼠的肾功能具有保护作用。生物信息学分析表明，肾缺血再灌注损伤过程中细胞焦亡（pyroptosis）通路显著激活；免疫组化实验结果证实，缺血再灌注损伤时肾脏细胞焦亡水平上调。给予SA可降低肾缺血再灌注损伤模型小鼠体内细胞焦亡相关蛋白焦孔素D（gasdermin D, GSDMD）、NLRP3、白细胞介素1β（interleukin-1β, IL-1β）的表达水平。体外（in vitro）与体内（in vivo）实验进一步证实，SA可通过抑制AKT/NLRP3信号通路发挥抗细胞焦亡作用。最终，SA可通过抑制AKT/NLRP3信号通路改善肾功能衰竭，从而减轻肾缺血再灌注损伤模型小鼠的肾脏损伤。