Fan Heng, Sun Min, Zhu Jian-Hua
Department of Intensive Care Unit, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang Province, P.R China.
Ren Fail. 2025 Dec;47(1):2472987. doi: 10.1080/0886022X.2025.2472987. Epub 2025 Mar 6.
Pyroptosis is considered to play an important role in the occurrence, development and prognosis of septic acute kidney injury (SAKI). We aimed to explore the specific molecular mechanism of S-nitrosoglutathione (SNG) regulating pyroptosis of kidney tubular epithelial cells (KTECs).
By constructing a mice model of sepsis, we pretreated them with SNG and used biochemical methods to detect the levels of serum inflammatory factors and mitochondrial reactive oxygen species (mtROS), assessed the severity of kidney injury and KTECs mitochondrial damage, and detected the expression of KTECs pyroptosis-related proteins and sirtuin 3 (SIRT3)/superoxide dismutase 2 (SOD2) pathway proteins.
The kidney injury caused by sepsis was significantly aggravated, and the levels of IL-1β, IL-6, IL-18, TNF-α, malondialdehyde (MDA) and mtROS were all increased, accompanied by the decrease of SIRT3 and SOD2 proteins, while NOD-like receptor with pyrin domain 3 (NLRP3), gasdermin D (GSDMD), Caspase-1 proteins expression and the number of KTECs apoptotic cells were all increased. However, after SNG pretreatment, the levels of IL-1β, IL-6, IL-18, TNF-α, MDA and mtROS were all significantly decreased, the expression of SIRT3 and SOD2 proteins were increased, NLRP3, GSDMD, Caspase-1 proteins expression and the number of KTECs apoptotic cells were decreased.
SNG protects SAKI by regulating the SIRT3/SOD2/mtROS signaling pathway to inhibit the pyroptosis of KTECs.
焦亡被认为在脓毒症急性肾损伤（SAKI）的发生、发展及预后中起重要作用。我们旨在探讨S-亚硝基谷胱甘肽（SNG）调节肾小管上皮细胞（KTECs）焦亡的具体分子机制。
通过构建脓毒症小鼠模型，用SNG对其进行预处理，采用生化方法检测血清炎症因子和线粒体活性氧（mtROS）水平，评估肾损伤严重程度及KTECs线粒体损伤情况，并检测KTECs焦亡相关蛋白及沉默调节蛋白3（SIRT3）/超氧化物歧化酶2（SOD2）信号通路蛋白的表达。
脓毒症所致肾损伤明显加重，白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、白细胞介素-18（IL-18）、肿瘤坏死因子-α（TNF-α）、丙二醛（MDA）和mtROS水平均升高，同时SIRT3和SOD2蛋白减少，而含pyrin结构域的NOD样受体3（NLRP3）、gasdermin D（GSDMD）、半胱天冬酶-1（Caspase-1）蛋白表达及KTECs凋亡细胞数量均增加。然而，SNG预处理后，IL-1β、IL-6、IL-18、TNF-α、MDA和mtROS水平均显著降低，SIRT3和SOD2蛋白表达增加，NLRP3、GSDMD、Caspase-1蛋白表达及KTECs凋亡细胞数量减少。
SNG通过调节SIRT3/SOD2/mtROS信号通路抑制KTECs焦亡，从而对SAKI起到保护作用。
