Inman Sharon R, Davis Nancy A, Olson Kristen M, Lukaszek Victoria A, McKinley Marc R, Seminerio Jennifer L
Department of Biomedical Sciences, Ohio University College of Osteopathic Medicine, Athens, Ohio 45701, USA.
Urology. 2003 Oct;62(4):750-4. doi: 10.1016/s0090-4295(03)00475-8.
To determine the effect of cyclosporine and rapamycin administration on renal function after ischemia/reperfusion injury (I/R). Cyclosporine A has known nephrotoxic effects. Thus, cyclosporine therapy subsequent to I/R injury may further exacerbate graft dysfunction. Rapamycin is a newer agent that suppresses the immune system by a different mechanism.
Male Wistar rats (250 g) were anesthetized, and the suprarenal aorta was clamped for 40 minutes. The right kidney was removed. After recovery, the rats were divided into four groups: group 1, controls, no ischemia and no treatment (n = 10); group 2, ischemia with no treatment (n = 8); group 3, ischemia plus rapamycin (0.17 mg/kg/day gavage, n = 8); and group 4, ischemia plus cyclosporine A (30 mg/kg/day intraperitoneally, n = 9). The glomerular filtration rate was measured 5 to 7 days after I/R injury using urinary iohexol clearance. Data are expressed as the mean +/- SEM, and intergroup comparisons were made using one-way analysis of variance.
The mean GFR value for the controls (no ischemia, no treatment) was 1.23 +/- 0.08 mL/min; for group 2 (ischemia, no treatment), it was 1.05 +/- 0.10 mL/min; for group 3 (ischemia plus rapamycin) 1.06 +/- 0.14 mL/min; and for group 4 (ischemia plus cyclosporine A) 0.44 +/- 0.06 mL/min (P <0.05 versus the other three groups). The mean arterial pressure was significantly lower in the ischemic rats treated with cyclosporine A (P <0.05 versus the other three groups).
After I/R injury, rapamycin may preserve renal function compared with cyclosporine treatment, because it does not have a direct vasoconstrictor effect on the renal microcirculation.
确定给予环孢素和雷帕霉素对缺血/再灌注损伤（I/R）后肾功能的影响。已知环孢素A具有肾毒性作用。因此，I/R损伤后进行环孢素治疗可能会进一步加重移植物功能障碍。雷帕霉素是一种新型药物，通过不同机制抑制免疫系统。
将雄性Wistar大鼠（250克）麻醉，夹闭肾上腹主动脉40分钟。切除右肾。恢复后，将大鼠分为四组：第1组为对照组，无缺血且未治疗（n = 10）；第2组为缺血未治疗组（n = 8）；第3组为缺血加雷帕霉素组（0.17毫克/千克/天灌胃，n = 8）；第4组为缺血加环孢素A组（30毫克/千克/天腹腔注射，n = 9）。在I/R损伤后5至7天，使用尿碘海醇清除率测量肾小球滤过率。数据以平均值±标准误表示，组间比较采用单因素方差分析。
对照组（无缺血，未治疗）的平均肾小球滤过率（GFR）值为1.23±0.08毫升/分钟；第2组（缺血，未治疗）为1.05±0.10毫升/分钟；第3组（缺血加雷帕霉素）为1.06±0.14毫升/分钟；第4组（缺血加环孢素A）为0.44±0.06毫升/分钟（与其他三组相比，P <0.05）。接受环孢素A治疗的缺血大鼠平均动脉压显著降低（与其他三组相比，P <0.05）。
I/R损伤后，与环孢素治疗相比，雷帕霉素可能会保护肾功能，因为它对肾微循环没有直接的血管收缩作用。
