Transplant Program, Medicine Faculty, National University of La Plata, La Plata, Argentina.
Clin Exp Immunol. 2012 Sep;169(3):330-7. doi: 10.1111/j.1365-2249.2012.04617.x.
Brain death (BD), a non-immunological factor of renal injury, triggers an inflammatory process causing pathological signs of cell death in the kidney, such as necrosis and apoptosis. Kidneys from brain dead donors show lower success rates than kidneys from living donors and one strategy to improve transplantation outcome is to precondition the donors. For the first time, anti-rat thymoglobulin (rATG) was administered in an experimental brain death animal model to evaluate if it could ameliorate histopathological damage and improve organ function. Animals were divided into three groups: V (n=5) ventilated for 2h; BD (n=5) brain death and ventilated for 2h; and BD+rATG (n=5) brain death, ventilated for 2h, rATG was administered during brain death (10mg/kg). We observed lower creatinine levels in treatment groups (means): V, 0·88±0·22 mg/dl; BD, 1·37±0·07 mg/dl; and BD+rATG, 0·64±0·02 mg/dl (BD versus BD+rATG, P<0·001). In the BD group there appeared to be a marked increase of ATN, whereas ATN was decreased significantly in the rATG group (V, 2·25±0·5 versus BD, 4·75±0·5, P<0·01; BD+rATG, 2·75±0·5 versus BD 4·75±0·5 P<0·01). Gene expression was evaluated with reverse transcription-polymerase chain reaction; tumour necrosis factor (TNF)-α, interleukin (IL)-6, C3, CD86 showed no significant difference between groups. Increased IL-10 and decreased CCL2 in BD+rATG compared to BD (both cases P<0·01). Myeloperoxidase was increased significantly after the brain death setting (V: 32±7·5 versus BD: 129±18). Findings suggest that rATG administered to potential donors may ameliorate renal damage caused by BD. These findings could contribute in the search for specific cytoprotective interventions to improve the quality and viability of transplanted organs.
脑死亡（BD）是肾脏损伤的非免疫因素，可引发炎症过程，导致肾脏细胞发生坏死和凋亡等病理性死亡迹象。脑死亡供体的肾脏移植成功率低于活体供体，改善移植效果的一种策略是对供体进行预处理。研究人员首次在实验性脑死亡动物模型中给予抗大鼠胸腺球蛋白（rATG），以评估其是否可以改善组织病理学损伤并改善器官功能。动物分为三组：V 组（n=5）通气 2 小时；BD 组（n=5）脑死亡并通气 2 小时；BD+rATG 组（n=5）脑死亡，通气 2 小时，rATG 在脑死亡期间给予（10mg/kg）。结果发现，治疗组的肌酐水平较低（平均值）：V 组为 0.88±0.22mg/dl；BD 组为 1.37±0.07mg/dl；BD+rATG 组为 0.64±0.02mg/dl（BD 组与 BD+rATG 组比较，P<0.001）。BD 组中急性肾小管坏死（ATN）明显增加，而 rATG 组中 ATN 显著减少（V 组为 2.25±0.5，BD 组为 4.75±0.5，P<0.01；BD+rATG 组为 2.75±0.5，BD 组为 4.75±0.5，P<0.01）。逆转录-聚合酶链反应评估基因表达；肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、C3、CD86 各组间无显著差异。与 BD 组相比，BD+rATG 组中 IL-10 增加，CCL2 减少（均 P<0.01）。脑死亡后髓过氧化物酶明显升高（V 组：32±7.5，BD 组：129±18）。结果表明，给予潜在供体 rATG 可改善脑死亡引起的肾脏损伤。这些发现可能有助于寻找特定的细胞保护干预措施，以提高移植器官的质量和活力。
