缺血预适应介导的内皮祖细胞对保留肾单位手术后肾功能的保护作用

Protective effect of endothelial progenitor cells mediated by ischemic preconditioning on renal ische-mic injury induced by nephron sparing surgery

目的探讨缺血预适应（IPC）介导的内皮祖细胞（EPCs）对保留肾单位手术（NSS）后肾功能的保护作用及其机制。方法90只雄性SD大鼠随机分为对照组（Sham）、保留肾单位组（NSS）、缺血预适应＋保留肾单位组（IPC），术后1、3、6、12、24h及3d观察大鼠肾功能变化、肾脏EPCs归巢、血管内皮增殖特征和血管生成因子蛋白表达。结果与NSS组比较，IPC组大鼠肾功能显著改善，肾小管损伤评分降低[（3．00_4-0．71）分比（1．80±0．45）分，P〈0．05]。恢复灌注12h后，IPC组肾脏EPCs含量高于同时期NSS组[（2．92±0．71）％比（5．75±0．71）％，P〈0．05]。与NSS组比较，IPC组大鼠肾小管周围毛细血管内皮细胞增殖以及肾脏组织中血管内皮生长因子（VEGF）、基质细胞衍生因子一1a（SDF一1a）蛋白表达均升高（P〈0．05）。结论NSS前给予IPC可对肾功能产生重要保护作用，机制可能与IPC介导EPCs归巢至损伤肾组织，并释放VEGF，促进肾小管周围毛细血管内皮细胞增殖相关。、

Objective To investigate the role of endothelial progenitor cells （EPCs） mediated by ischemic preconditioning （IPC） in renal ischemic injury in a nephron sparing surgery （NSS） rat model. Methods Ninety male Sprague-Dawley rats were randomly divided into three groups after right-side kidney nephrectomy. In sham-operated rats, lumbotomy without vascular clamping was performed; In NSS rats, renal blood vesses were clamped for 40 min and lower pole partial nephrectomy （ PN ） was performed ; In NSS ＋ IPC rats, besides pre-treatment with 15-min ischemia and 10-min reperfusion, the rest procedures were the same as those in NSS rats. At 1, 3, 6, 12, 24 h, and 3 days after reperfusion, the circulating pool and kidneys were harvested. The severity of renal injury, the home of EPCs, proliferation of endotheli- al cells as well as vascular growth factor expression was examined. Results Pretreated rats exhibited signif- icant improvements in renal function and morphology： The histological score was significantly decreased in IPC group as compared with NSS group [ （ 1.80± O. 45 ） vs. （ 3.00±O. 71 ）, P 〈 0. 05 ]. The number of EPCs in the kidneys was increased at 12 h after reperfusion in IPC group as compared with NSS groups [ （5. 75 ± 0. 71 ） % vs. （ 2. 92±0. 71 ） %, P 〈 0. 05 ]. Proliferation of EPCs in peritubular capillaries was markedly increased in the kidneys treated with IPC. In addition, the expression of vascular endothelial growth factor, and stromal cell-derived factor-1 ct in the kidneys of pretreated rats was increased as com- pared with that in rats subjected to ischemic injury （P 〈 0. 05 ）. Conclusion IPC may attenuate renal is- chemic injury induced by NSS; EPCs play an important role in renal protection, which involves promotion of endothelial cell proliferation through release of several angiogenic factors.