Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P. R. China.
Ren Fail. 2022 Dec;44(1):1769-1779. doi: 10.1080/0886022X.2022.2134028.
Renal injury is a fatal complication in critically ill patients with sepsis. As an ultrashort-acting synthetic opioid derivative, remifentanil has been reported to mitigate renal injury and sepsis. Nevertheless, whether remifentanil also suppresses sepsis-triggered renal injury is uncertain. The aim of this study was to investigate the effect of remifentanil on endoplasmic reticulum stress (ERS) and inflammatory response in an lipopolysaccharide (LPS)-stimulated renal tubular epithelial cell (HK-2) model and its mechanism. The viability of HK-2 cells with the absence or presence of LPS treatment was surveyed by cell counting kit-8 assay. Under the condition of LPS treatment, apoptosis was appraised by TUNEL assay and western blot. Levels of inflammatory factors were estimated though corresponding kits. Western blot tested the expression of toll-like receptor 4 (TLR4)/nuclear factor-kappaB (NF-κB) signaling-associated proteins. Also, the expression of ERS-related proteins was detected by western blot. Further, ERS inducer tunicamycin (TM) was added and the aforementioned experiments were conducted again. The results underlined the protective effects of remifentanil on LPS-evoked viability injury, inflammation, activation of TLR4/NF-κB signaling and ERS in HK-2 cells. Moreover, the impacts of remifentanil on the biological events of LPS-insulted HK-2 cells were all reversed by TM administration. To conclude, remifentanil might have a remarkable ameliorative effect on sepsis-induced renal injury, which implied the potential of remifentanil-based drug therapy in sepsis-induced renal injury.
肾损伤是脓毒症危重症患者的致命并发症。瑞芬太尼作为一种超短效合成阿片类药物衍生物，已被报道可减轻肾损伤和脓毒症。然而，瑞芬太尼是否也抑制脓毒症引起的肾损伤尚不确定。本研究旨在探讨瑞芬太尼对脂多糖（LPS）刺激的肾小管上皮细胞（HK-2）模型内质网应激（ERS）和炎症反应的影响及其机制。通过细胞计数试剂盒-8 测定法检测有无 LPS 处理时 HK-2 细胞的活力。在 LPS 处理条件下，通过 TUNEL 测定法和蛋白质印迹法评估细胞凋亡。通过相应的试剂盒评估炎症因子水平。蛋白质印迹法检测 Toll 样受体 4（TLR4）/核因子-κB（NF-κB）信号相关蛋白的表达。此外，通过蛋白质印迹法检测 ERS 相关蛋白的表达。进一步加入 ERS 诱导剂衣霉素（TM）并再次进行上述实验。结果表明，瑞芬太尼对 LPS 诱导的 HK-2 细胞活力损伤、炎症、TLR4/NF-κB 信号激活和 ERS 具有保护作用。此外，瑞芬太尼对 LPS 损伤 HK-2 细胞的生物学事件的影响均被 TM 给药逆转。总之，瑞芬太尼可能对脓毒症引起的肾损伤具有显著的改善作用，这暗示了基于瑞芬太尼的药物治疗在脓毒症引起的肾损伤中的潜在应用价值。
