Research Article

选择性NLRP3-炎症小体抑制剂CY-09通过抑制NLRP3-炎症小体活化来改善糖尿病肾病的肾损伤

卷 30, 期 28, 2023

发表于: 23 November, 2022

页: [3261 - 3270] 页: 10

弟呕挨: 10.2174/0929867329666220922104654

价格: $65

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摘要

背景:糖尿病肾病(DN)是糖尿病最严重的并发症之一,也是导致终末期肾病(ESRD)的主要原因。 NLRP3 炎症小体的激活已被证明在 DN 的发展中起重要作用。因此,NLRP3 炎性体组装的特异性和直接靶标可能具有治疗潜力。 CY-09 是一种新的 NLRP3 炎症小体特异性抑制剂,已被证明可通过抑制 NLRP3 炎症小体的激活来预防非酒精性脂肪肝疾病 (NAFLD)。然而,其在肾脏疾病,尤其是 DN 中的作用尚未见报道。 方法: 本研究采用HE染色评估各组肾脏病理损伤,RT-PCR、免疫荧光和WB检测炎症蛋白和纤维化蛋白的表达变化。 TUNEL染色检测细胞凋亡水平。 结果:在这里,我们显示 db/db 小鼠的炎症、氧化应激、细胞凋亡和纤维化增加,而 CY-09 通过抑制 NLRP3 炎性体激活发挥肾脏保护作用。在体外,CY-09 还以剂量依赖的方式抑制 NLRP3 并减少 caspase-1、IL-18、IL-1β 和细胞凋亡。 结论:CY-09通过抑制NLRP3炎性体有效保护肾脏免受高血糖引起的损伤,可能是一种很有前景的预防DKD进展的治疗策略。

关键词: NLRP3炎症小体,CY-09DN,炎症,肾脏病理,高血糖症。

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