Department of Nephrology, State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China.
Nephron Exp Nephrol. 2013;124(3-4):19-27. doi: 10.1159/000357380. Epub 2014 Jan 8.
The therapeutic use of the antineoplastic drug cisplatin (DDP) in the elderly is limited by its nephrotoxic effects. The aim of this study was to examine the effect of short-term calorie restriction (CR) on DDP-induced nephrotoxicity in aged rats.
A group of 25-month-old male Sprague-Dawley rats were divided into two groups: ad libitum (AL) and CR, which were fed 60% of the food consumed by AL rats for 8 weeks. The two groups were each further randomly divided into two subgroups: OAL control, OAL+DDP, OCR control, and OCR+DDP. A single dose of DDP (6 mg/kg) was injected intraperitoneally. Functional and structural changes of the kidneys were evaluated quantitatively by biochemical, histopathological, and morphometric analyses.
At the end of the 8 weeks, rats in the OCR group lost 14.8% more body mass than rats in the OAL group. Pretreatment with CR had several effects: (1) it reduced the levels of blood urea nitrogen and serum creatinine, (2) it reduced the magnitude of the renal tubular epithelial damage, and (3) it significantly reduced the incidence of activated caspase-3 and TUNEL-positive cells in kidneys injured by DDP. However, SIRT1 had the opposite trend after DDP application between the two groups.
Short-term CR exhibits a renoprotective effect in experimental DDP-induced renal injury, the mechanism of which may involve CR antiapoptotic effects and promotion of SIRT1.
抗肿瘤药物顺铂（DDP）在老年人中的治疗应用受到其肾毒性的限制。本研究旨在探讨短期热量限制（CR）对老年大鼠 DDP 诱导肾毒性的影响。
将一组 25 月龄雄性 Sprague-Dawley 大鼠分为两组：自由进食（AL）和 CR，CR 组大鼠的食物摄入量为 AL 组的 60%，持续 8 周。两组进一步随机分为两组：OAL 对照组、OAL+DDP 组、OCR 对照组和 OCR+DDP 组。单次腹腔注射 DDP（6mg/kg）。通过生化、组织病理学和形态计量学分析定量评估肾脏的功能和结构变化。
在 8 周结束时，OCR 组大鼠的体重比 OAL 组大鼠减轻了 14.8%。CR 预处理有以下几种作用：（1）降低血尿素氮和血清肌酐水平；（2）减轻肾小管上皮损伤程度；（3）显著降低 DDP 损伤肾脏中激活的 caspase-3 和 TUNEL 阳性细胞的发生率。然而，DDP 应用后两组间 SIRT1 的趋势相反。
短期 CR 对实验性 DDP 诱导的肾损伤具有肾脏保护作用，其机制可能涉及 CR 抗细胞凋亡作用和促进 SIRT1。
