目的探讨缺血预适应(IPC)对肾脏缺血再灌注损伤(IR)后内源性内皮祖细胞(EPC)归巢动力学的影响及意义。方法60只雄性sD大鼠切除右肾1周后被随机分为3组:(1)对照组:仅游离左肾动脉;(2)缺血再灌注损伤组(IR组):夹闭左肾动脉40min后恢复灌注;(3)缺血预适应组(IPC组):夹闭肾蒂前给予15min缺血、10min再灌注预处理,余同IR组。术后3、12、24、72h留取大鼠静脉血、肾、脾、肺脏。血生化检测及组织病理学检查评估各组大鼠术后肾损伤程度;流式细胞术观察IPC对EPC归巢动力学影响。结果IPC组血肌酐、尿素氮及肾小管损伤评分均低于同时间点IR组。与对照组或IR组相比,1PC组大鼠外周血EPC数量在术后12、24h升高(P〈0.05);与同时间点IR组比较,IPC组肾组织EPC数量在12、24h增高[(11.36±0.66)%比(6.37±0.69)%,(6.31±0.70)%比(4.40±0.60)%,均P〈0.051;IPC组术后12h肺脏EPC数量高于IR组[(2.95±0.66)%比(1.78±0.59)%,P〈0.05]及对照组[(2.95±0.66)%比(1.66±0.61)%,P〈0.05]。IPC组术后72h脾脏EPC数量高于同时间点IR组和对照组[(0.55±0.06)%比(0.34±0.07)%、(0.31±0.06)%,均P〈0.05]。结论IPC可动员内源性EPC随血流归巢至损伤肾脏。EPC尚可在肺脏、脾脏中聚集。
Objectives To investigate the impact of ischemic preconditioning (IPC) on dynamics of homing of endothelial progenitor cells (EPCs) after renal isehemia reperfusion injury (IR). Methods Sixty male Sprague- Dawley rats were randomly divided into three groups after right-side kidney nephrectomy: for sham-operated rats, lumbotomy without vascular clamping was performed; IR rats were clamped renal blood vessels for 40 minutes while IPC rats were pre- treated with 15 min ischemia and 10 min reperfusion. At 3, 12, 24 h, and 3 days after reperfusion, the pool of circulating, kidneys, lungs and spleens were harvested. The extent of renal injury was assessed by biochemical and histological examination. The dynamics of homing of EPCs was observed by flow cytometry. Results The rats in IPC group exhibited significant improvements in renal function and morphology. Compared with IR group and sham group, the number of EPCs in blood was increased in the IPC group at 12 h and 24 h after reperfusion (P 〈 0.05). The number of EPCs in kidney was increased at all times point in the IPC group and IR group as compared to the sham group (P 〈 0.05. In addition, EPCs number was increased in IPC group compared with the IR group at 12 h and 24 h [(11.36±0.66)% vs (6.37±0.69)%, (6.31±0.70)% vs (4.40±0.60)%, all P 〈 0.05]. Compared with IR group and sham group, the number of EPCs in the lung was increased in the IPC groups at 12 h after reperfusion [(2.95±0.66)% vs (1.78±0.59)%, (1.66±0.61)%, all P 〈 0.05]. The number of EPCs in spleen was increased in the IPC group at 72 h as compared with the IR group and sham group [(0.55±0.06)% vs (0.34±0.07)%, (0.31± 0.06)%, all P 〈 0.05]. Conclusions Endogenous EPCs may home to injnred kidney after IPC. EPCs can also gather in the lungs and spleen.