促红细胞生成素对急性肾损伤中干细胞因子及其受体表达的影响

Erythropoietin effects on expression of stem cell factor and its receptor in acute renal injury

背景:细胞因子在减轻肾脏缺血再灌注损伤中的作用日益受到重视,干细胞因子具有造血系统以外的器官保护作用。目的:探讨大鼠急性肾损伤模型中干细胞因子及其受体c-Kit表达的变化和促红细胞生成素预处理对其表达的影响。方法:成年雄性Wistar大鼠34只,采用夹闭双侧肾蒂建立缺血再灌注模型,缺血45 min后再灌注24 h,随机分为假手术组(n=10)、缺血再灌注组(n=12)和促红细胞生成素组(n=12),促红细胞生成素组于造模前2 h一次性尾静脉注射重组人促红细胞生成素5 000 U/kg。免疫组化及图像分析技术检测各组肾组织中干细胞因子及c-Kit的表达变化,测定血清肌酐和尿素氮水平,苏木精-伊红染色观察肾组织病理学改变并计算肾小管损伤积分。结果与结论:干细胞因子及c-Kit在肾组织中的表达仅限于肾小管区域。与假手术组比较,干细胞因子和c-Kit在缺血再灌注组和促红细胞生成素组的表达均明显增高(P<0.05),促红细胞生成素组干细胞因子表达高于缺血再灌注组(P<0.01),但两组c-Kit表达差异无显著性意义(P>0.05);促红细胞生成素组血清肌酐与尿素氮水平明显低于缺血再灌注组(P<0.05),但高于假手术组(P<0.05)。与缺血再灌注组比较,促红细胞生成素组肾组织病变减轻。说明缺血再灌注导致急性肾损伤发生时干细胞因子及c-Kit表达升高,而促红细胞生成素对急性肾损伤的保护作用可能与上调干细胞因子及c-Kit表达有关。

BACKGROUND： The effects of cytokines on lessening ischemia/reperfusion injury to the kidney have been paid attention increasingly. Stem cell factor has protective effects on organs except hematopoietic system.OBJECTIVE： To study the expression of stem cell factor and its receptor c-Kit in acute kidney injury model of rat, and the effect of erythropoietin on the expression of stem cell factor and c-Kit.METHODS： A total of 34 adult male Wistar rats were selected to induce ischemia/reperfusion models by occluding bilateral renal pedicle （ischemia for 45 minutes and reperfusion for 24 hours）. The animals were randomly divided into sham-operation group （n=10）, ischemia/reperfusion group （n=12） and erythropoietin group （n=12）. In the erythropoietin group, 5 000 U/kg recombinant human erythropoietin was injected once via the tail vein at 2 hours before modeling. The expression of stem cell factor and c-Kit was detected by immunohistochemistry and image analysis technique in each group. The serum concentrations of creatinine and blood urea nitrogen were measured. Meanwhile, renal pathologic changes were observed by hematoxylin-eosin staining, and renal tubule injury integral was calculated.RESULTS AND CONCLUSION： Stem cell factor and c-Kit were detected only in the renal tubule section. The expression of stem cell factor and c-Kit in the ischemia/reperfusion group and erythropoietin group was higher than sham-operation group （P 〈 0.05）. The expression of stem cell factor was higher in the erythropoietin group than that in the ischemia/reperfusion group （P 〈 0.01）. However, no significant difference in c-Kit was detected between the two groups （P 〉 0.05）. Serum creatinine and urea nitrogen levels were significantly lower in the erythropoietin group than that in the ischemia/reperfusion group （P 〈 0.05）, but higher than that in the sham-operation group （P 〈 0.05）. Compared with the ischemia/reperfusion group, pathological changes in nephridial tissue were more lessened in the erythropoietin group. These results suggested that stem cell factor and c-Kit expression increased when ischemia/reperfusion led to acute renal injury. The protective effect of erythropoietin on acute renal injury possibly associated with the upregulation of stem cell factor and c-Kit expression.