促红细胞生成素对大鼠肾间质纤维化发动蛋白-1表达影响

目的 探讨促红细胞生成素(EPO)对大鼠肾间质纤维化发动蛋白-1（Drp-1）表达的影响。方法 81只SD大鼠，分为假手术组、对照组和EPO组，每组各27只。EPO组、对照组采用单侧输尿管结扎并剪断建立肾间质纤维化模型，假手术组仅游离输尿管而不结扎和剪断；EPO组予EPO皮下注射；假手术组和对照组给予等量生理盐水皮下注射。各组于术后7、14和21 d取动脉血分离血清检测血肌酐和尿素氮水平。取梗阻侧肾组织行苏木精-伊红和Masson染色，观察肾脏病理学变化。用免疫组化方法检测肾组织Drp-1的表达。结果 ①EPO组各时点血清肌酐和尿素氮水平显著低于对照组（P<0.01），但高于假手术组（P<0.05）。②EPO组各时点肾组织病理改变较对照组明显减轻，肾小管间质损伤评分和肾间质纤维化相对面积均低于对照组（P均<0.05），但高于假手术组（P<0.05）。③EPO组肾组织的Drp-1表达显著低于对照组（P<0.05），但高于假手术组（P<0.05）。结论 Drp-1在大鼠肾间质纤维化肾组织中表达增加，参与肾脏纤维化过程；EPO可以通过抑制Drp-1表达，从而延缓肾间质纤维化的进展。

Effects of erythropoietin on the expression of dynamin related protein-1 in renal interstitial fibrosis rats

Objective To observe the expression of dynamin related protein-1（Drp-1） of the renal interstitial tissue in rat model induced by unilateral ureteral obstruction (UUO) and the renoprotective effect of erythroprietin. Methods Renal interstitial fibrosis rat model was produced by unilateral ureteral obstruction, eighty-one rats were randomly allocated to shame operation group, UUO model group and treated group. After operation rats in treated group were given subcutaneous injection with erythroprietin 3 000 U·kg-1 once a week until rats were sacrificed. Rats in sham-operated group and UUO model group were given subcutaneous injection with identical normal saline. In each group, nine rats were chosen randomly to be sacrificed at the 7th , 14th and 21st day after operation for histological examination. Renal tissues were examined by HE and Masson stain. Immunhistochemistry was performed for Drp-1 in the renal interstitum. Results The renal function (serum Cr and BUN) damage in treatment group was lower than that in the model group at day 21(P<0.01), and obviously higher than the sham group (P<0.05). Compared with the UUO model group, the score of the renal interstitial damage and fibrotic area of treated group was decreased markedly at three time points（P<0.05, respectively). The scores of the renal interstitial damage and fibrotic area of treatment group were higher than those of the sham group (P<0.05). The expression of Drp-1 of treated group was decreased markedly at three time points（P<0.05) compared with the UUO model group, and was increased compared with sham group(P<0.05). Conclusion The expression of Drp-1 increased during rat renal interstitial fibrosis. Erythroprietin maybe alleviates the degree of renal interstitial fibrosis by down -regulating the expression of Drp-1.