Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Drug Dev Res. 2022 May;83(3):659-668. doi: 10.1002/ddr.21897. Epub 2021 Nov 23.
Parecoxib is a selective COX-2-specific inhibitor, which has been demonstrated to inhibit sepsis-induced systemic inflammation, but its role in sepsis-induced acute kidney injury has not been studied. This study was designed to investigate the effects of Parecoxib on sepsis-induced acute kidney injury. In this study, the mice sepsis model was established using an internationally recognized cecal ligation and puncture (CLP). Hematoxylin-eosin staining was performed to examine kidney injury. Biochemical kit was used to detect the expression of BUN and Cre in serum, and ELISA was used to detect the expression of inflammatory factors in renal tissue. Tunel staining was used to detect tissue apoptosis. Furthermore, CCK-8 assay was used to detect the cell viability of HK-2 cells and RT-qPCR was used to detect the expression of LPS-induced inflammatory factors in HK-2 cells.TUNEL staining was used to detect the level of cell apoptosis. Finally, the expressions of COX-2, p-NF-kB P65, p-IKKβ, NF-kB P65, IKKβ, Kim1, NGAL, iNOS, VEGF, VEGFR2, CD31 and apoptosis-related proteins in renal tissues and HK-2 cells were detected by Western blot. We discovered that parecoxib could alleviate renal pathological changes, reduce renal function injury, and inhibit renal pathology to inhibit the release of inflammatory factors in renal tissue. Parecoxib inhibited sepsis induced microvascular damage and apoptosis in renal tissue. Parecoxib reduced the inflammation and apoptosis of renal tubular epithelial cells induced by LPS. Our data suggest that Parecoxib ameliorates sepsis-induced kidney injury, and may have potential as a novel therapeutic method for treating sepsis-induced kidney injury.
帕瑞昔布是一种选择性 COX-2 特异性抑制剂，已被证明可抑制脓毒症引起的全身炎症反应，但它在脓毒症引起的急性肾损伤中的作用尚未得到研究。本研究旨在探讨帕瑞昔布对脓毒症引起的急性肾损伤的影响。在这项研究中，使用国际公认的盲肠结扎和穿孔（CLP）建立了小鼠脓毒症模型。进行苏木精-伊红染色以检查肾损伤。使用生化试剂盒检测血清中 BUN 和 Cre 的表达，使用 ELISA 检测肾组织中炎症因子的表达。Tunel 染色用于检测组织细胞凋亡。此外，使用 CCK-8 测定法检测 HK-2 细胞的细胞活力，并使用 RT-qPCR 检测 HK-2 细胞中 LPS 诱导的炎症因子的表达。TUNEL 染色用于检测细胞凋亡水平。最后，通过 Western blot 检测肾组织和 HK-2 细胞中 COX-2、p-NF-κB P65、p-IKKβ、NF-κB P65、IKKβ、Kim1、NGAL、iNOS、VEGF、VEGFR2、CD31 和凋亡相关蛋白的表达。我们发现帕瑞昔布可减轻肾脏病理变化，减轻肾功能损伤，并抑制肾组织中炎症因子的释放，从而抑制肾组织中炎症因子的释放。帕瑞昔布抑制脓毒症诱导的肾组织微血管损伤和细胞凋亡。帕瑞昔布减少了 LPS 诱导的肾小管上皮细胞的炎症和凋亡。我们的数据表明，帕瑞昔布可改善脓毒症引起的肾脏损伤，可能具有作为治疗脓毒症引起的肾脏损伤的新的治疗方法的潜力。
