National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
J Cell Physiol. 2021 Feb;236(2):931-945. doi: 10.1002/jcp.29903. Epub 2020 Jun 24.
Ischemia reperfusion (I/R)-induced acute kidney injury (AKI) is a common and serious condition. Irisin, an exercise-induced hormone, improves mitochondrial function and reduces reactive oxygen species (ROS) production. Glutathione peroxidase 4 (GPX4) is a key regulator of ferroptosis and its inactivation aggravates renal I/R injury by inducing ROS production. However, the effect of irisin on GPX4 and I/R-induced AKI is still unknown. To study this, male adult mice were subjected to renal I/R by occluding bilateral renal hilum for 30 min, which was followed by 24 hr reperfusion. Our results showed serum irisin levels were decreased in renal I/R mice. Irisin (250 μg/kg) treatment alleviated renal injury, downregulated inflammatory response, improved mitochondrial function, and reduced ER stress and oxidative stress after renal I/R, which were associated with upregulation of GPX4. Treated with RSL3 (a GPX4 inhibitor) abolished irisin's protective effect. Thus, irisin attenuates I/R-induced AKI through upregulating GPX4.
缺血再灌注（I/R）引起的急性肾损伤（AKI）是一种常见且严重的情况。鸢尾素是一种运动诱导的激素，可改善线粒体功能并减少活性氧（ROS）的产生。谷胱甘肽过氧化物酶 4（GPX4）是铁死亡的关键调节因子，其失活通过诱导 ROS 产生加重肾脏 I/R 损伤。然而，鸢尾素对 GPX4 和 I/R 诱导的 AKI 的影响尚不清楚。为了研究这一点，雄性成年小鼠通过夹闭双侧肾门 30 分钟来进行肾脏 I/R，然后再进行 24 小时再灌注。我们的结果表明，肾脏 I/R 小鼠的血清鸢尾素水平降低。鸢尾素（250μg/kg）治疗可减轻肾脏损伤，下调炎症反应，改善线粒体功能，并减少肾脏 I/R 后的内质网应激和氧化应激，这与 GPX4 的上调有关。用 RSL3（一种 GPX4 抑制剂）处理可消除鸢尾素的保护作用。因此，鸢尾素通过上调 GPX4 来减轻 I/R 引起的 AKI。
