1 Department of Surgery, University of Salamanca, Salamanca, Spain. 2 Biosanitary Research Institute (IBSAL), Salamanca Spain. 3 Digna Biotech, Madrid, Spain. 4 Department of Nephrology, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain. 5 Renal and Cardiovascular Physiopathology Unit, Department of Physiology and Pharmacology, University of Salamanca, Salamanca, Spain. 6 Queen Sofía Institute for Renal Research, Renal Foundation, Madrid, Spain. 7 Address correspondence to: José M. Lopez-Novoa Ph.D., Renal and Cardiovascular Physiopathology Unit, Department of Physiology and Pharmacology, University of Salamanca, Edificio Departamental, Campus Unamuno, 37007 Salamanca, Spain.
Transplantation. 2013 Dec 27;96(12):1034-42. doi: 10.1097/TP.0b013e3182a74db4.
Ischemia-reperfusion injury (IRI) remains a major problem in renal transplantation, and the inflammatory response to IRI exacerbates the resultant renal injury. We have investigated whether the systemic administration of cardiotrophin-1 (CT-1) is able to improve renal function and to decrease inflammatory responses in a rat model of renal IRI.
IRI was induced by renal pedicle clamping (60 min) followed by reperfusion and contralateral nephrectomy. CT-1 was injected through the penile vein 30 min before clamping release and its effects were compared with a saline-treated group at five different time points of reperfusion.
Survival in the CT-1-treated group was higher than in the untreated group and prevented IRI-induced reduction in the glomerular filtration rate, as shown by blunted increases in creatinine and urea plasma levels and less severe decrease in creatinine clearance. These effects of CT-1 seem to be mediated by reduction in oxygen-radical production, increased superoxide dismutase expression, attenuation of neutrophil and macrophage infiltration, lower adhesion molecule expression, lower inflammation demonstrated by a decrease of plasma levels of proinflammatory cytokine secretion such as tumor necrosis factor-α, interleukin-1β and interferon-γ, lower inducible nitric oxide synthase expression and lower nuclear factor-κB activation, and reduced apoptosis.
Therefore, these results suggest that CT-1 administration prevents IRI and it might be used as a therapeutic strategy to protect the kidney against IRI.
缺血再灌注损伤（IRI）仍然是肾移植中的一个主要问题，IRI 引发的炎症反应会加重由此导致的肾损伤。我们研究了心脏营养素-1（CT-1）的全身给药是否能够改善肾IRI 大鼠模型的肾功能并减少炎症反应。
通过夹闭肾蒂（60 分钟）然后再灌注和对侧肾切除术来诱导 IRI。在夹闭释放前 30 分钟通过阴茎静脉注射 CT-1，并在再灌注的五个不同时间点将其作用与盐水处理组进行比较。
与未治疗组相比，CT-1 治疗组的存活率更高，并防止了 IRI 引起的肾小球滤过率降低，表现为肌酐和尿素血浆水平升高幅度降低，肌酐清除率降低幅度较小。CT-1 的这些作用似乎是通过减少氧自由基的产生、增加超氧化物歧化酶的表达、减弱中性粒细胞和巨噬细胞浸润、降低粘附分子的表达、降低促炎细胞因子如肿瘤坏死因子-α、白细胞介素-1β和干扰素-γ的血浆水平来实现的，从而减轻炎症，降低诱导型一氧化氮合酶的表达和核因子-κB 的激活，并减少细胞凋亡。
因此，这些结果表明 CT-1 的给药可预防 IRI，并且它可能被用作保护肾脏免受 IRI 的治疗策略。
