Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, P.R. China.
Department of Cardiovascular Medicine, Nanjing Chest Hospital, Nanjing, P.R. China.
Anticancer Res. 2020 Feb;40(2):635-643. doi: 10.21873/anticanres.13993.
BACKGROUND/AIM: Contrast-induced AKI (CI-AKI) is an important clinical complication of intravascular use of iodinated contrast agents. The aim of the present study was to investigate the renoprotective effect of Apela on contrast-induced acute kidney injury.
Blood samples from patients exposed to iodinated contrast agent were collected to assay for Apela and creatinine levels. The effects of ELA32 (Apela 32) on iodixanol-induced apoptosis, inflammation response, mitochondrial ROS production and DNA damage were examined in NRK-52E renal tubular epithelial cells.
Plasma Apela levels were decreased in patients exposed to the contrast agent. Iodixanol-induced apoptosis was reduced in ELA32 treated NRK-52E cells (p<0.05). ELA32 treatment inhibited iodixanol-induced mitochondrial ROS generation (p<0.01). Iodixanol-induced inflammatory cytokines TNFa and IL-6 and inflammatory genes Nrf2 and ICAM-1 were reduced by ELA32 treatment (p<0.01). Reduced Apela expression in iodixanol-treated cells was partially restored by ELA32 treatment (p<0.05). ELA32 treatment suppressed iodixanol-induced up-regulation of DNA damage-associated gene P-ATR and p-CHK1 as well as apoptosis-associated gene C-caspase 3 (p<0.05).
Administration of iodinated contrast agent reduces Apela expression. ELA32 treatment reduces iodixanol-induced apoptosis, inflammatory response and mitochondrial and DNA damage in renal tubular epithelial cells.
背景/目的：对比剂诱导的急性肾损伤（CI-AKI）是血管内使用碘造影剂的一种重要临床并发症。本研究旨在探讨 Apela 对对比剂诱导的急性肾损伤的肾保护作用。
收集暴露于碘造影剂的患者的血样，检测 Apela 和肌酐水平。在 NRK-52E 肾小管上皮细胞中，研究了 ELA32（Apela 32）对碘克沙醇诱导的细胞凋亡、炎症反应、线粒体 ROS 产生和 DNA 损伤的影响。
暴露于造影剂的患者血浆 Apela 水平降低。ELA32 处理可减少碘克沙醇诱导的 NRK-52E 细胞凋亡（p<0.05）。ELA32 处理可抑制碘克沙醇诱导的线粒体 ROS 生成（p<0.01）。ELA32 处理可降低碘克沙醇诱导的 TNFa 和 IL-6 炎症细胞因子以及 Nrf2 和 ICAM-1 炎症基因的表达（p<0.01）。碘克沙醇处理细胞中 Apela 表达的降低部分被 ELA32 处理所恢复（p<0.05）。ELA32 处理可抑制碘克沙醇诱导的与 DNA 损伤相关基因 P-ATR 和 p-CHK1 以及与细胞凋亡相关基因 C-caspase 3 的上调（p<0.05）。
给予碘造影剂可降低 Apela 表达。ELA32 处理可减少碘克沙醇诱导的肾小管上皮细胞凋亡、炎症反应以及线粒体和 DNA 损伤。
