Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
1] Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK [2] Department of Anesthesiology, Taihe Hospital, Hubei University of Medicine, Hubei, China.
Kidney Int. 2014 Jan;85(1):112-23. doi: 10.1038/ki.2013.334. Epub 2013 Sep 11.
Chronic allograft nephropathy (CAN) is a common finding in kidney grafts with functional impairment. Prolonged hypothermic storage-induced ischemia-reperfusion injury is associated with the early onset of CAN. As the noble gas xenon is clinically used as an anesthetic and has renoprotective properties in a rodent model of ischemia-reperfusion injury, we studied whether early treatment with xenon could attenuate CAN associated with prolonged hypothermic storage. Exposure to xenon enhanced the expression of insulin growth factor-1 (IGF-1) and its receptor in human proximal tubular (HK-2) cells, which, in turn, increased cell proliferation. Xenon treatment before or after hypothermia-hypoxia decreased cell apoptosis and cell inflammation after reoxygenation. The xenon-induced HK-2 cell proliferation was abolished by blocking the IGF-1 receptor, mTOR, and HIF-1α individually. In the Fischer-to-Lewis rat allogeneic renal transplantation model, xenon exposure of donors before graft retrieval or recipients after engraftment enhanced tubular cell proliferation and decreased tubular cell death and cell inflammation associated with ischemia-reperfusion injury. Compared with control allografts, xenon treatment significantly suppressed T-cell infiltration and fibrosis, prevented the development of CAN, and improved renal function. Thus, xenon treatment promoted recovery from ischemia-reperfusion injury and reduced susceptibility to the subsequent development of CAN in allografts.
慢性移植肾肾病（CAN）是移植肾功能损害的常见表现。长时间低温保存导致的缺血再灌注损伤与 CAN 的早期发病有关。由于稀有气体氙在临床上被用作麻醉剂，并且在缺血再灌注损伤的啮齿动物模型中具有肾脏保护作用，我们研究了早期氙治疗是否可以减轻与长时间低温保存相关的 CAN。氙暴露可增强人近端肾小管（HK-2）细胞中胰岛素样生长因子-1（IGF-1）及其受体的表达，进而增加细胞增殖。低温-缺氧前后的氙处理可减少再复氧后的细胞凋亡和细胞炎症。单独阻断 IGF-1 受体、mTOR 和 HIF-1α 可消除氙诱导的 HK-2 细胞增殖。在 Fischer 到 Lewis 大鼠同种异体肾移植模型中，供体在获取移植物前或受体在移植后暴露于氙气可增强肾小管细胞增殖，减少与缺血再灌注损伤相关的肾小管细胞死亡和细胞炎症。与对照同种异体移植物相比，氙气处理显著抑制了 T 细胞浸润和纤维化，预防了 CAN 的发展，并改善了肾功能。因此，氙气处理促进了缺血再灌注损伤的恢复，并降低了同种异体移植物随后发生 CAN 的易感性。
