粒细胞集落刺激因子动员骨髓内皮祖细胞对急性肾损伤的修复作用  

Granulocyte colony stimulating factors repair acute renal injury by mobilizing endothelial progenitor cells from the bone marrow in mice

作　　者：易俊[1] 申翼[1] 罗立国[1] 胡若愚[1] 李好[1] 景华[1] 

机构地区：[1]第二军医大学南京临床医学院(南京军区南京总医院)心胸外科,南京医学博士研究生210002

出　　处：《医学研究生学报》2012年第7期685-693,共9页Journal of Medical Postgraduates

基　　金：国家自然科学基金(30972969)

摘　　要：目的急性肾损伤(acute kidney injury,AKI)影响肾内皮细胞的结构和功能,所以内皮的修复是AKI治疗的重要靶点。观察应用粒细胞集落刺激因子(granulocyte colony stimulating factor,G-CSF)对由内毒素诱导的AKI小鼠外周血中内皮祖细胞(endothelial progenitor cells,EPCs)的数量、骨髓源性EPCs的增殖能力,以及向肾组织中归巢的影响。并观察由骨髓动员的EPCs对肾损伤的修复作用。方法健康CD-1雄性小鼠30只,随机分为假手术组(A组)、肾损伤对照组(B组)和G-CSF预处理肾损伤组(C组),每组10只。观察各组小鼠肾功能以及肾组织形态学变化、炎性因子水平、外周血中EPCs数量、肾组织细胞凋亡指数、CD34+和胎肝激酶-1(fetla liver kinase 1,FLK-1+)阳性细胞的表达。并获取小鼠骨髓,分离、培养EPCs,检测EPCs的增殖、迁移和黏附能力。结果 B组和C组小鼠肾功能受损,炎性反应、肾组织学改变前者比后者重(P<0.05);外周血EPCs含量B组比A组多,明显比C组少,肾组织CD34和FLK阳性细胞的表达B组比A组多,但少于C组(P<0.05);肾细胞凋亡指数B组最高(P<0.05);B组骨髓来源的EPCs数量比A组多,但增殖能力和迁移能力与A组比较差异无统计学意义,各指标均明显低于C组(P<0.05)。结论 G-CSF可降低AKI小鼠炎性反应的水平,有效动员骨髓来源的EPCs,并促进其增殖和迁移,增加外周血EPCs含量,对AKI小鼠肾功能起到保护作用。Objective Acute kidney injury （AKI） impairs the structure and function of renal endothelial cells. Repairing endothelial cell function may represent an important therapeutic target. This study aimed to investigate the effects of the granulocyte colony stimulating factor （G-CSF） on endothelial progenitor cells （EPCs） and renal function in the rat model of AKI. Methods We equally randomized 30 healthy CD-1 male mice into groups A （sham operation）, B （acute renal injury） and C （G-CSF）. We ob- served changes in renal function and histomorphology, counts of EPCs and renal apoptotic cells, inflammatory factors, and expressions of CD34 and FLK-1 positive ceils. We isolated EPCs from the bone marrow of the mice with the density gradient centrifugation method for detection of the effects of G-CSF on the proliferation, migration, and adhesion of EPCs. Results Renal function injury, inflammatory reaction and histological changes were significantly more obvious in group B than in C （ P 〈0. 05 ）. EPCs in the peripheral blood were evidently more in group B than that in A, but fewer than that in C, and so were CD34 and FLK positive cells in the renal tissue （P 〈 0. 05）. The apoptosis of renal cells was the highest in group B （P 〈 0.05）. The number of EPCs from the bone marrow was higher in group B than that in A, with no significant differences in their abilities of proliferation and migration between the two, and all these indexes were significantly lower than in group C （P 〈 0.05）. Conclusion G-CSF could reduce inflammatory reaction in AKI mice by rapid mobilization of EPCs from the bone marrow, promote their proliferation and migration, increase their content in the peripheral blood, and protect the renal function of AKI mice.

关 键 词：内皮祖细胞 粒细胞集落刺激因子 炎性因子 急性肾损伤 

分 类 号：R692[医药卫生—泌尿科学]