Department of Kidney Transplantation, Nephropathy Hospital, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Traditional Chinese Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Mol Med Rep. 2019 Oct;20(4):3337-3346. doi: 10.3892/mmr.2019.10576. Epub 2019 Aug 8.
The mechanisms by which prostaglandin E2 receptor 4 (EP4) protects against renal ischemia‑reperfusion (I/R) injury (IRI) remain to be fully elucidated. In the present study, the protective effects of EP4 signaling on renal mitochondria and against renal IRI, as well as the underlying mechanisms, were investigated. A rat model of renal IRI was established. The right kidney was separated without damaging the artery clip, and the renal blood perfusion was then restored after 60 min. One group of animals was treated with EP4 agonists prior to I/R. The mitochondrial mass, the copy number of mitochondrial (mt)DNA, adenosine triphosphate (ATP) production and mitochondrial autophagy were analyzed. It was identified that renal IRI reduced the mitochondrial mass, decreased the mtDNA copy number and inhibited ATP production. The loss of renal mitochondria was attributed to the excessive mitochondrial autophagy induced by renal IRI. Pre‑treatment with EP4 agonist inhibited excessive mitochondrial autophagy, the loss of mitochondria and maintained and the energy imbalance within the cells. It was indicated that renal IRI causes excessive mitochondrial autophagy, which is one of the important causes of renal dysfunction.
前列腺素 E2 受体 4 (EP4) 防止肾缺血再灌注 (IRI) 损伤的机制仍未完全阐明。在本研究中，研究了 EP4 信号对肾线粒体的保护作用及其对肾 IRI 的作用机制。建立了大鼠肾 IRI 模型。分离右肾而不损伤动脉夹，然后在 60 分钟后恢复肾血液灌注。一组动物在 I/R 前用 EP4 激动剂治疗。分析线粒体质量、线粒体 (mt)DNA 的拷贝数、三磷酸腺苷 (ATP) 生成和线粒体自噬。研究发现，肾 IRI 降低了线粒体质量，降低了 mtDNA 拷贝数并抑制了 ATP 的生成。肾线粒体的丧失归因于肾 IRI 引起的过度线粒体自噬。EP4 激动剂预处理抑制了过度的线粒体自噬、线粒体的丧失以及细胞内的能量失衡。结果表明，肾 IRI 导致过度的线粒体自噬，这是肾功能障碍的重要原因之一。
