红细胞生成素对单侧输尿管梗阻大鼠肾组织补体C3及肾小管上皮间充质转分化的影响  

Effects of Erythropoietin on Complement 3 and Epithelial-to-Mesenchymal Transition of Renal Tissue in Unilateral Uretreal Obstructire Rats

作　　者：傅槟槟[1] 张凤霞[1] 万建新[1] 崔炯[1] 许艳芳[1] 尤丹瑜[1] 

机构地区：[1]福建医科大学附属第一医院肾内科,福州350005

出　　处：《中国药学杂志》2012年第16期1292-1296,共5页Chinese Pharmaceutical Journal

基　　金：福建省卫生厅青年科研基金(2008-2-23)

摘　　要：目的探讨红细胞生成素对单侧输尿管梗阻大鼠肾脏纤维化的影响及其机制。方法建立单侧输尿管梗阻大鼠模型,并把实验动物分成假手术组(对照组)、单侧输尿管梗阻组、单侧输尿管梗阻大鼠红细胞生成素小剂量治疗组(100 u.kg-1.d-1红细胞生成素,小剂量组)和单侧输尿管梗阻大鼠红细胞生成素大剂量治疗组(1 000 u.kg-1.d-1红细胞生成素,大剂量组)。在单侧输尿管梗阻术后第3～14天隔天腹膜内注射红细胞生成素,所有大鼠在第14天处死;观察肾组织病理变化;免疫组化检测各组大鼠肾组织α-平滑肌肌动蛋白、上皮细胞钙黏蛋白和补体C3的表达。结果与单侧输尿管梗阻组比较,单侧输尿管梗阻大鼠用红细胞生成素治疗后,梗阻侧肾脏胶原纤维含量明显减少,且大剂量红细胞生成素治疗组减少更明显。与对照组比较,单侧输尿管梗阻组大鼠梗阻侧肾脏肾小管上皮细胞α-平滑肌肌动蛋白大量表达,肾小管上皮细胞钙黏蛋白表达明显减弱,并可见肾小管上皮细胞大量表达C3。与单侧输尿管梗阻组比较,单侧输尿管梗阻大鼠用红细胞生成素治疗后,梗阻侧肾脏肾小管上皮细胞C3和α-平滑肌肌动蛋白表达明显减弱,上皮细胞钙黏蛋白表达明显增强,以上改变在大剂量红细胞生成素治疗组更加明显。结论红细胞生成素可抑制单侧输尿管梗阻大鼠肾小管上皮间充质转分化,减轻肾间质纤维化,这种作用可能与其抑制肾小管上皮细胞补体C3的表达有关。OBJECTIVE To investigate the effects of erythropoietin （EPO） on renal fibrosis of unilateral uretreal obstruction （UUO） rats and its mechanism. METHODS The model of renal fibrosis was established by UUO procedure in rats. Experimental rats were randomly divided into 4 groups： sham operation group （control group）, UUO group, 100 u·kg^-1·d^-1 EPO treatment group （low dosage group） and 1 000 u·kg^-1·d^-1EPO treatment group （high dosage group）. The rats in control group and UUO group were given physiological saline, and those in UUO treatment group were given EPO by intraperitoneal injection from 3 to 14 d after establishment of UUO model. All rats were given methane to induce anesthesia and consequently executed. The patblogical change of renal tissue was observed, and immunohistochemistry was performed to measure the expressions of α-SMA, E-cadherin and comple- ment 3 （C3） in renal tissue. RESULTS Compared with UUO group, renal fibrosis were attenuated by EPO treatment, especially in high dosage group. Compared with control group, the expressions of α-SMA and C3 were significantly up-regulated, and the expres- sions of E-cadherin were significantly down-regulated in UUO group. In contrast, EPO treatment significantly attenuated the up-regula- tion of C3 and α-SMA and the down-regulation of E-cadherin in renal tissue, and these changes were more obvious in UUO rats treated with high dosage of EPO. CONCLUSION EPO can inhibit EMT and attenuate renal fibrosis in obstructed kidney. It is suggested that the renoprotective effects of EPO are probably related with inhibition of C3 expression in renal tubular epithelial cells .

关 键 词：红细胞生成素 补体C3 肾脏纤维化 上皮间充质转分化 单侧输尿管梗阻 肾小管上皮细胞 

分 类 号：R965[医药卫生—药理学]