Lin Meihua, Wu Xi, Zhang Shuang
Department of Nephrology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China.
Department of Surgery, Qingdao Hospital, University of Health and Rehabilitation Sciences (Qingdao Municipal Hospital), Qingdao 266071, China.
Pathol Res Pract. 2025 Feb;266:155807. doi: 10.1016/j.prp.2024.155807. Epub 2024 Dec 30.
Inflammation is one of the most significant pathological changes in ischemia-reperfusion injury (IRI). Sufentanil has protective effects on IRI by reducing inflammatory responses. This study aimed to investigate the protective effects and possible mechanisms of sufentanil on renal IRI (RIRI). In this study, sufentanil inhibited hypoxia/reoxygenation (H/R)-treated HK-2 proliferation and apoptosis, decreased cleaved caspase3 and increased B-cell Lymphoma 2 (Bcl-2) protein expression, inhibited reactive oxygen species (ROS) generation, and reduced inflammatory factor secretion. Moreover, sufentanil inhibited KCNQ1 overlapping transcript 1 (KCNQ1OT1) expression in H/R-treated HK-2 cells, and pcDNA-KCNQ1OT1 reversed the cell protective effects of sufentanil, whereas miR-211-5p inhibitor here reversed the effects of pcDNA-KCNQ1OT1. Furthermore, miR-211-5p targets the 3'UTR of high mobility group box1 (HMGB1), and HMGB1 reversed the inhibitory effects of miR-211-5p mimic or sufentanil on cell proliferation, apoptosis, oxidative stress, and inflammation. Mechanistic studies revealed that sufentanil alleviated H/R-treated HK-2 cell injury was mediated by inhibiting the toll like receptor 4 (TLR4)/ myeloid differentiation factor 88 (MyD88)/ nuclear factor kappa B (NF-κB) pathway. In renal ischemia-reperfusion (I/R) rats, sufentanil inhibited KCNQ1OT1, HMGB1 and cleaved caspase3 expression, promoted miR-211-5p expression and alleviated inflammatory infiltration in renal tissues.
炎症是缺血再灌注损伤（IRI）中最显著的病理变化之一。舒芬太尼通过减轻炎症反应对IRI具有保护作用。本研究旨在探讨舒芬太尼对肾缺血再灌注损伤（RIRI）的保护作用及可能机制。在本研究中，舒芬太尼抑制缺氧/复氧（H/R）处理的HK-2细胞增殖和凋亡，降低裂解的半胱天冬酶3水平并增加B细胞淋巴瘤2（Bcl-2）蛋白表达，抑制活性氧（ROS）生成，并减少炎症因子分泌。此外，舒芬太尼抑制H/R处理的HK-2细胞中KCNQ1重叠转录本1（KCNQ1OT1）的表达，而pcDNA-KCNQ1OT1逆转了舒芬太尼的细胞保护作用，而此处的miR-211-5p抑制剂则逆转了pcDNA-KCNQ1OT1的作用。此外，miR-211-5p靶向高迁移率族蛋白B1（HMGB1）的3'非翻译区（UTR），HMGB1逆转了miR-211-5p模拟物或舒芬太尼对细胞增殖、凋亡、氧化应激和炎症的抑制作用。机制研究表明，舒芬太尼减轻H/R处理的HK-2细胞损伤是通过抑制Toll样受体4（TLR4）/髓样分化因子88（MyD88）/核因子κB（NF-κB）途径介导的。在肾缺血再灌注（I/R）大鼠中，舒芬太尼抑制KCNQ1OT1、HMGB1和裂解的半胱天冬酶3表达，促进miR-211-5p表达并减轻肾组织中的炎症浸润。
