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Xinxin Chen,1 Huan Tong,2 Yu Chen,3 Chaosheng Chen,1 Jingjing Ye,2 Qingfei Mo,2 Guangju Zhao,2 Guangliang Hong,2 Chenfei Zheng,1 Zhongqiu Lu2 1Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; 2Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; 3Department of Nephrology, Wenzhou Hospital of Traditional Chinese Medicine Affiliated with Zhejiang Chinese Medical University, Wenzhou, Zhejiang, China Background: The role of Klotho (KL) in sepsis-induced acute kidney injury (AKI) and the potential relationship between KL and autophagy in septic AKI were investigated. Materials and methods: A murine model of sepsis-induced AKI was established by cecal ligation and puncture (CLP). Mice undergoing CLP and immortalized proximal tubular epithelial human HK-2 cells that were exposed to lipopolysaccharide (LPS) were treated with recombinant KL, autophagy stimulator rapamycin (Rap), and autophagy suppressor 3-methyladenine (3-MA). Results: Autophagy activation and KL reduction reached maximum levels in mice 24 hours after CLP. Recombinant KL and/or Rap significantly attenuated CLP-induced renal dysfunction (P |