Kidney Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang, Hangzhou, China.
Acta Physiol (Oxf). 2024 Sep;240(9):e14211. doi: 10.1111/apha.14211. Epub 2024 Jul 29.
A myokine secreted by skeletal muscles during exercise called irisin mitigates ischemia-reperfusion (I/R) injury in epithelial cells of various organs by limiting damage to mitochondria. We test whether irisin may preserve the mitochondrial integrity and function in renal tubular epithelial cells and protect against ischemia-reperfusion-induced acute kidney injury (AKI).
We correlated serum irisin levels with serum creatinine and BUN levels from both AKI patients and healthy individuals. In mice with irisin administration, various renal injury markers such as serum creatinine, BUN, kidney injury molecule-1 (Kim-1), and neutrophil gelatinase-associated lipocalin (NGAL), and renal histopathology were assessed after I/R. To identify the potential mechanisms of the protective of irisin's protective effect, we perfused proximal tubules under confocal microscopy and analyzed kidney tissues by qPCR, western blot, and immunohistochemistry.
Serum irisin correlated inversely with serum creatinine and BUN levels were significantly lower in AKI patients than in healthy subjects. Administering irisin to mice after I/R decreased biomarker levels for AKI including serum creatinine, BUN, Kim-1, NAGL and lessened histological changes. In kidney tissues of mice, irisin upregulated the mitochondrial autophagy marker protein microtubule-associated protein 1 light chain 3 (LC3), the mitochondrial autophagy pathway-related proteins PTEN-induced putative kinase 1 (PINK1) and Parkinson's disease 2 parkin (PARK2) and downregulated the reactive substrate protein sequestosome 1 (P62) and mitochondrial membrane proteins translocase of outer mitochondrial membrane 20 (TOM20) and translocase of inner mitochondrial membrane 23 (TIM23).
Irisin protects against renal I/R injury, which may involve the preservation of mitochondrial integrity and function.
运动时由骨骼肌分泌的一种肌因子叫鸢尾素，它通过限制线粒体损伤，减轻各种器官上皮细胞的缺血再灌注（I/R）损伤。我们检测鸢尾素是否可以维持肾小管上皮细胞中线粒体的完整性和功能，并防止缺血再灌注引起的急性肾损伤（AKI）。
我们将 AKI 患者和健康个体的血清鸢尾素水平与血清肌酐和 BUN 水平进行了相关分析。在给予鸢尾素的小鼠中，在 I/R 后评估了各种肾损伤标志物，如血清肌酐、BUN、肾损伤分子-1（Kim-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL），以及肾组织病理学。为了确定鸢尾素保护作用的潜在机制，我们在共聚焦显微镜下灌注近端肾小管，并通过 qPCR、western blot 和免疫组织化学分析肾组织。
血清鸢尾素与血清肌酐和 BUN 水平呈负相关，AKI 患者的血清水平明显低于健康个体。在 I/R 后给予小鼠鸢尾素可降低 AKI 的生物标志物水平，包括血清肌酐、BUN、Kim-1、NAGL，并减轻组织学变化。在小鼠的肾组织中，鸢尾素上调了线粒体自噬标志物蛋白微管相关蛋白 1 轻链 3（LC3）、线粒体自噬途径相关蛋白 PTEN 诱导的假定激酶 1（PINK1）和帕金森病 2 parkin（PARK2），并下调了反应底物蛋白 sequestosome 1（P62）和线粒体外膜转位酶 20（TOM20）和内膜转位酶 23（TIM23）。
鸢尾素可防止肾 I/R 损伤，这可能涉及到线粒体完整性和功能的维持。
