Lemoine Sandrine, Pillot Bruno, Rognant Nicolas, Augeul Lionel, Rayberin Maud, Varennes Annie, Laville Maurice, Ovize Michel, Juillard Laurent
1 INSERM UMR-1060, Laboratoire CarMeN, Université Lyon 1, Lyon, France. 2 Nephrology Department, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. 3 Anatomopathology, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France. 4 Biology Department, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France. 5 Nephrology Department, Hospices Civils de Lyon, CHLS, Pierre Bénite, France. 6 Service d'Explorations Fonctionnelles Cardiovasculaires, Hospices Civils de Lyon, Louis Pradel Hospital, Lyon, France.
Transplantation. 2015 Apr;99(4):717-23. doi: 10.1097/TP.0000000000000530.
Ischemia-reperfusion (IR) injury leads to mitochondrial permeability transition pore opening, which contributes to cell death. The aim of this study is to determine whether ischemic or pharmacological postconditioning with cyclosporine A (CsA) might protect the kidney from lethal reperfusion injury.
Male mice underwent a unilateral (right) nephrectomy followed by 30 minutes of contralateral (left) clamping of the renal artery. We studied 4 groups at 20 minutes and 24 hours of reperfusion: a sham group (n = 4), an ischemic group (n = 6), CsA-postconditioned group (postcond-CsA, injection of 3 mg/kg of CsA 5 minutes before the end of ischemia, (n = 6), and an ischemic postconditioning (IPC) group (n = 6), consisting of 3 cycles of 30 seconds of renal ischemia with 30 seconds intervening reperfusion. After 24 hours of reperfusion, we measured plasma creatinine, urea, and histological kidney injury. The kidney mitochondria were isolated to assess the mitochondria calcium retention capacity and oxidative phosphorylation.
At 24 hours after reperfusion, serum creatinine decreased in postcond-CsA and IPC compared to ischemic group. The histological score was also significantly improved with postcond-CsA and IPC. At 20 minutes and 24 hours of reperfusion, calcium retention capacity was decreased significantly in the ischemic group. The mitochondrial respiration stay decreased in the ischemic group at 24 hours of reperfusion, whereas the respiration was improved significantly in the postcond-CsA and IPC group. Bax and cleaved caspase 3 decreased in PostCsA and IPC group.
Our results suggest that IPC and CsA, administered immediately before reperfusion, protect the kidney from lethal injury.
缺血再灌注（IR）损伤会导致线粒体通透性转换孔开放，进而促使细胞死亡。本研究旨在确定缺血预处理或用环孢素A（CsA）进行药物后处理是否能保护肾脏免受致命性再灌注损伤。
雄性小鼠接受单侧（右侧）肾切除术，随后对侧（左侧）肾动脉夹闭30分钟。我们在再灌注20分钟和24小时时研究了4组：假手术组（n = 4）、缺血组（n = 6）、CsA后处理组（后处理-CsA组，在缺血结束前5分钟注射3 mg/kg的CsA，n = 6）以及缺血后处理（IPC）组（n = 6），该组由3个周期组成，每个周期包括30秒的肾脏缺血和30秒的中间再灌注。再灌注24小时后，我们测量了血浆肌酐、尿素以及肾脏组织学损伤情况。分离肾脏线粒体以评估线粒体钙保留能力和氧化磷酸化。
再灌注24小时后，与缺血组相比，后处理-CsA组和IPC组的血清肌酐降低。后处理-CsA组和IPC组的组织学评分也显著改善。再灌注20分钟和24小时时，缺血组的钙保留能力显著降低。再灌注24小时时，缺血组的线粒体呼吸持续下降，而后处理-CsA组和IPC组的呼吸则显著改善。后处理-CsA组和IPC组中Bax和裂解的半胱天冬酶3减少。
我们的结果表明，在再灌注前立即给予IPC和CsA可保护肾脏免受致命性损伤。
