Parra C, Salas P, Dominguez J
Departamento de Urologia, Pontificia Universidad Católica de Chile, Santiago, Chile.
Transplant Proc. 2010 Jan-Feb;42(1):245-7. doi: 10.1016/j.transproceed.2009.11.018.
Recent evidence has demonstrated that the immune response and, more specifically, lymphocytes (T and B) and dendritic cells participate as mediators of renal ischemia reperfusion injury (IRI). The aim of this study was, therefore, to evaluate the effect of various immunosuppressive drugs with known activity to prevent IRI among rats undergoing a scheme that is potentially applicable in the clinic.
Male Sprague-Dawley rats (200-300 g) underwent 60 minutes of ischemia by renal artery clamping and contralateral nephrectomy. The experimental groups (n = 6-7) were as follows: I, Sham; II, Control; III, Rapamycin (R; 1 mg/kg); IV, Methylprednisolone (M; 15 mg/kg); V, Vitamin D3 (VD3; 2 microg/kg); VI, VD3 (1 microg/kg); and VII, M (15 mg/kg) + R (1 mg/kg). Each drug was administered in 2 doses at 6 hours and 1 hour before surgery. Creatinine (Cr) was determined on days 0.1, 2, 3, 5, and 7, and Cr clearance was determined on days 3 and 7. At 7 days nephrectomy was performed to obtain samples for histology to evaluate the degree of acute tubular necrosis.
Mortality from renal insufficiency was between 0 and 33%, except in group V (66%; 4/6; P = .01). Kidney function was similar to controls in all groups except for creatinine at 7 days between group VI (VD3) and control (1.05 vs 0.65; P < .05) but no difference in Cr clearance. Histologically moderate to severe renal damage was greater in groups V and VI (VD3) than controls (P = .04).
We observed that none of the drugs conferred protection against IRI in a time setting relevant to kidney transplantation. Controversy exists regarding R, because some prior studies have shown a deleterious effect on IRI injury, although we did not observe any deleterious effect.
最近的证据表明，免疫反应，更具体地说，淋巴细胞（T细胞和B细胞）和树突状细胞作为肾缺血再灌注损伤（IRI）的介质发挥作用。因此，本研究的目的是评估各种具有已知活性的免疫抑制药物对接受一种可能适用于临床的方案的大鼠预防IRI的效果。
雄性Sprague-Dawley大鼠（200-300克）通过肾动脉夹闭和对侧肾切除术进行60分钟的缺血。实验组（n = 6-7）如下：I组，假手术组；II组，对照组；III组，雷帕霉素（R；1毫克/千克）；IV组，甲泼尼龙（M；15毫克/千克）；V组，维生素D3（VD3；2微克/千克）；VI组，VD3（1微克/千克）；VII组，M（15毫克/千克）+R（1毫克/千克）。每种药物在手术前6小时和1小时分2剂给药。在第0、1、2、3、5和7天测定肌酐（Cr），并在第3天和第7天测定Cr清除率。在第7天进行肾切除术以获取组织学样本，以评估急性肾小管坏死的程度。
除V组（66%；4/6；P = 0.01）外，肾功能不全导致的死亡率在0%至33%之间。除VI组（VD3）与对照组在第7天的肌酐水平外（1.05对0.65；P < 0.05），所有组的肾功能与对照组相似，但Cr清除率无差异。组织学上，V组和VI组（VD3）的中度至重度肾损伤比对照组更严重（P = 0.04）。
我们观察到，在与肾移植相关的时间范围内，没有一种药物能对IRI起到保护作用。关于雷帕霉素存在争议，因为一些先前的研究表明它对IRI损伤有有害作用，尽管我们没有观察到任何有害作用。
