红细胞生成素对慢性肾衰竭大鼠残肾组织归巢因子表达的影响

目的 观察红细胞生成素(EPO)对慢性肾衰竭(CRF)大鼠肾组织归巢因子表达的影响.方法 采用分阶段5/6肾切除制备大鼠CRF模型.实验动物随机分为3组:假手术组、CRF模型组和EPO治疗组.从第3周开始,治疗组大鼠每次皮下注射重组人EPO 50 IU/kg,每周3次,共6周.8周后检测各组大鼠血肌酐(Scr)、血尿素氮(BUN)、尿蛋白、血红蛋白(Hb)；采用实时荧光定量PCR、Western印迹和免疫组化方法检测残肾组织EPO及其受体(EPOR)、归巢因子及其受体(SDF-1、CXCR4、Ang-1、Tie2、SCF、c-Kit)的表达.结果 与模型组比较,EPO治疗可上调残肾组织归巢因子及其受体(SDF-1、CXCR4、Ang-1、Tie2、SCF、c-Kit)mRNA和蛋白的表达(均P＜0.05)；同时,EPO治疗还可上调残肾组织EPO及EPOR的mRNA和蛋白的表达(均P＜ 0.05).此外,EPO治疗还能下调大鼠Scr、BUN和尿蛋白水平(均P＜0.05),上调Hb水平(P＜0.05).结论 EPO能改善慢性肾衰竭大鼠的肾功能,这种作用可能与其激活残肾组织归巢因子而参与损伤肾脏的修复有关.

Effect of erythropoietin on the expression of homing factors of remnant renal tissue from rats with chronic renal failure

Objective To investigate the effect of erythropoietin (EPO) on the expression of homing factors of remnant renal tissue from rats with chronic kidney failure (CRF). Methods The CRF model was established by a two stage 5/6 nephrectomy procedure in rats. Experimental rats were randomly divided into three groups: sham operation group, CRF model group, EPO treatment group (CRF rats treated with human recombinant EPO). CRF rats received EPO by hypodermic injection with 50 IU/kg three times a week for 6 weeks and then were sacrificed. Serum creatinine (Scr), blood urea nitrogen (BUN), urine protein and haematoglobin (Hb) were measured. The expression of EPO and its receptor (EPOR), homing factors and their receptors (SDF-1, CXCR4, Ang-1, Tie2, SCF, c-Kit) in remnant kidney tissue were detected by the methods of real - time PCR, Western blotting and immunohistochemistry. Results Compared with CRF model group, the expressions of homing factors and their receptors (SDF-1, CXCR4, Ang-1, Tie2, SCF, c-Kit ) in remnant kidney tissue were up- regulated by administration of EPO in treatment group (all P＜0.05). Meanwhile, the expressions of EPO and its receptor in remnant kidney tissue were also up- regulated by administration of EPO in treatment group (all P＜0.05). Moreover, the Scr, BUN and urine protein in EPO treatment group were lower than those in CRF model group (all P＜0.05). Instead, haematoglobin was higher than that in CRF model group (P＜0.05). Conclusion EPO can improve renal function in rats with chronic renal failure, maybe through activation of homing factors in remnant kidney tissue which are involved in repairing damaged kidney.