Timsit Marc Olivier, Gadet Rudy, Ben Abdennebi Hassen, Codas Ricardo, Petruzzo Palmina, Badet Lionel
Department of Urology and Transplantation, Hôpital Edouard Herriot, Lyon, France.
J Urol. 2008 Jul;180(1):388-91. doi: 10.1016/j.juro.2008.02.043. Epub 2008 May 21.
We determined the role of ischemic preconditioning on renal function and histology in a rat model.
A total of 34 Sprague-Dawley rats (Janvier Laboratories, Le Genet-St-Isle, France) were divided into 6 groups, including sham operation, ischemic preconditioning alone (5 minutes of bilateral ischemia followed by 5 minutes of reperfusion for 3 cycles), ischemia alone (60 minutes of bilateral renal pedicle clamping), ischemic preconditioning before bilateral ischemia, ischemic preconditioning before ischemia in left nephrectomized rats and ischemic preconditioning of the left kidney alone before 60 minutes of bilateral warm ischemia to assess the effect of left kidney preconditioning on the contralateral kidney. Serum creatinine and malondialdehyde levels were recorded at days 0, 1, 3, 11 and 15. Kidneys were harvested at day 15 for histological study and alpha-smooth muscle actin typing.
At days 1 and 3 serum creatinine and malondialdehyde levels were significantly lower in the ischemic preconditioning group compared to levels in the ischemia alone group. At days 11 and 15 creatinine and malondialdehyde levels were similar in all groups and comparable to levels at day 0. At day 15 ischemic preconditioning kidneys showed significantly decreased fibrosis and alpha-smooth muscle actin expression than ischemia alone kidneys.
Ischemic preconditioning improves the ability of rat kidney to tolerate subsequent ischemic injury in the first 3 days after reperfusion. Moreover, fibrosis and alpha-smooth muscle actin expression are decreased in ischemic preconditioning kidneys 15 days after reperfusion, suggesting a potential interest of ischemic preconditioning in surgical situations that expose kidneys to prolonged warm ischemia.
我们在大鼠模型中确定了缺血预处理对肾功能和组织学的作用。
总共34只斯普拉格-道利大鼠(法国勒热内-圣伊勒的扬维耶实验室)被分为6组,包括假手术组、单纯缺血预处理组(双侧缺血5分钟,随后再灌注5分钟,共3个周期)、单纯缺血组(双侧肾蒂夹闭60分钟)、双侧缺血前缺血预处理组、左肾切除大鼠缺血前缺血预处理组以及双侧温暖缺血60分钟前仅对左肾进行缺血预处理组,以评估左肾预处理对侧肾的影响。在第0、1、3、11和15天记录血清肌酐和丙二醛水平。在第15天摘取肾脏进行组织学研究和α-平滑肌肌动蛋白分型。
在第1天和第3天,缺血预处理组的血清肌酐和丙二醛水平显著低于单纯缺血组。在第11天和第15天,所有组的肌酐和丙二醛水平相似,且与第0天的水平相当。在第15天,缺血预处理的肾脏与单纯缺血的肾脏相比,纤维化和α-平滑肌肌动蛋白表达显著降低。
缺血预处理可提高大鼠肾脏在再灌注后前3天耐受后续缺血损伤的能力。此外,再灌注15天后,缺血预处理的肾脏纤维化和α-平滑肌肌动蛋白表达降低,这表明缺血预处理在使肾脏暴露于长时间温暖缺血的手术情况中可能具有潜在意义。