Abstract

Sepsis is a life-threatening disorder that develops in response to an infection. Kidneys are one of the most common organs affected by sepsis. This study explored the influence of Sestrin2 regulating NLRP3 inflammasome activation on sepsis-induced renal injury. A sepsis mouse model was established by intraperitoneal injection of LPS. Adenoviral transduction was used to upregulate Sestrin2 expression. H&E staining, TUNEL staining, DHE staining, ELISA, RT-PCR, and western blotting were applied to the detections of pathological changes, ROS, oxidative stress markers, Sestrin2 expression, apoptosis-related proteins, and NLRP3 inflammasome-related factors in renal tissues. A HK-2 cell model of LPS-induced injury was constructed, and the release of IL-6 and TNF-α and expression of NLRP3 were detected using ELISA and immunofluorescence, respectively. Sestrin2 overexpression suppressed inflammation and reduced renal injury and apoptosis in LPS-treated mice. Moreover, overexpressed Sestrin2 resulted in inhibited levels of ROS, NLRP3, caspase-1, and IL-1β in renal tissues, as well as reduced TNF-α and IL-6 secretion and NLRP3 expression in LPS-stimulated HK-2 cells. Collectively, Sestrin2 can inhibit inflammation and reduce sepsis-induced renal injury, which may be associated with NLRP3 inflammasome inactivation and oxidative stress reduction.

中文翻译：

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Sestrin2 通过抑制 NLRP3 激活和活性氧产生来减轻脓毒症引起的肾损伤

摘要

脓毒症是一种因感染而发生的危及生命的疾病。肾脏是最常见受脓毒症影响的器官之一。本研究探讨了 Sestrin2 调节 NLRP3 炎性体激活对脓毒症所致肾损伤的影响。通过腹腔注射LPS建立脓毒症小鼠模型。腺病毒转导用于上调 Sestrin2 表达。采用H&E染色、TUNEL染色、DHE染色、ELISA、RT-PCR、western blotting检测肾组织病理变化、ROS、氧化应激标志物、Sestrin2表达量、凋亡相关蛋白、NLRP3炎症小体相关因子。构建LPS损伤的HK-2细胞模型，采用ELISA和免疫荧光法分别检测IL-6和TNF-α的释放以及NLRP3的表达。Sestrin2 过表达可抑制 LPS 处理小鼠的炎症并减少肾损伤和细胞凋亡。此外，过表达的Sestrin2导致肾组织中ROS、NLRP3、caspase-1和IL-1β的水平受到抑制，以及LPS刺激的HK-2细胞中TNF-α和IL-6的分泌以及NLRP3表达的减少。总的来说，Sestrin2 可以抑制炎症并减少脓毒症引起的肾损伤，这可能与 NLRP3 炎性体失活和氧化应激减少有关。