irisin通过激活自噬介导了RIPC对肾脏缺血再灌注损伤的保护作用

远端缺血预适应(remote limb ischemic preconditioning, RIPC)能保护肾脏缺血再灌注(ischemia/reperfusion, I/R)损伤，研究提示这可能与体液因子释放入血有关。Irisin是一种肌肉分泌的内分泌因子，其在调节能量代谢、物质平衡等方面发挥重要作用。预实验发现血浆irisin在RIPC后升高，且对肾脏I/R损伤有保护作用。自噬对于减轻肾脏I/R损伤有着重要作用， AMPK是介导细胞自噬的关键环节。预实验显示irisin可激活细胞自噬，伴有AMPK激活。由此我们提出假设“irisin介导了RIPC对肾脏I/R损伤的保护作用，而这种作用是通过激活AMPK诱导细胞自噬而发挥作用的”。本实验以C57BL/6J小鼠、FNDC5-/-小鼠以及肾脏近曲小管细胞为研究对象，明确irisin介导了RIPC对肾脏I/R损伤的保护作用，并探讨该作用的机制。

Remote limb ischemic preconditioning (RIPC) exerts protective effect on renal ischemia/reperfusion (I/R) injury. Previous studies suggested that this effect might induced by some humoral factor in circulation. Irisin is a muscle-origin humoral factor, it plays a key role in energy metabolism and material balance. Our preliminary experiment found that plasma concentration of irisin was increased after treatment of remote limb ischemic preconditioning, and irisin could also protect renal I/R injury. It has been proved autophagy may protect renal I/R injury. Irisin activates intracellular AMPK, which contributes to regulate cell autophagy. Our preliminary experiment showed that irisin could activate autophagy with activation of AMPK. So we proposed “irisin mediates the protective effect of RIPC on renal I/R injury via activation of AMPK and inducing autophagy”. This study will use C57BL/6J mice, FNDC5-/-mice and renal proximal tubule cells as research objects to determine that irisin mediates the protective effect of RIPC on renal I/R injury and to discover the mechanism.