南方医科大学学报 ›› 2014, Vol. 34 ›› Issue (01): 65-.

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嘌呤霉素氨基核苷肾病肾脏中RANK-RANKL的表达

冯仲林,刘双信,史 伟,肖厚勤,梁馨苓,刘晓颖,叶智明,王素霞,梁永正,章 斌,王文健,刘艳辉,梅 平,徐丽霞,马建超,夏运风   

  • 出版日期:2014-01-20 发布日期:2014-01-20

Renal expression of RANK-RANKL in a rat model of puromycin aminonucleoside
nephropathy

  • Online:2014-01-20 Published:2014-01-20

摘要: 目的探讨RANK-RANKL在嘌呤霉素氨基核苷肾病(PAN)大鼠动物模型肾脏中的表达。方法36只SD大鼠被分配为
PAN组及对照组,单次静脉注射嘌呤霉素氨基核苷(PA,100 mg/kg)制作PAN动物模型。大鼠于第3、7、14天检测蛋白尿及血肌
酐。检测肾脏病理,并分析RANK和RANKL变化。结果(1)在PAN SD大鼠动物模型中,第3、7、14天时蛋白尿与对照组比较
有显著差别,第7天达到高峰;(2)用Western blotting及RT-PCR定量检测发现RANK-RANKL蛋白及mRNA在PAN模型组高
于对照组;(3)用激光共聚焦技术显示足细胞标记蛋白Synaptopodin与RANK完全重合,提示RANK主要在足细胞表达;(4)免
疫电镜发现RANK在PAN模型组明显增多,且主要定位于足突的顶部胞膜和胞质内。结论在PAN SD大鼠动物模型足细胞异
常表达RANK-RANKL,提示RANK及RANKL在足细胞损伤中可能发挥重要作用。

Abstract: Objective To investigate RANK-RANKL expression in the kidneys of a rat model of puromycin aminonucleoside
nephropathy (PAN). Methods Thirty-six SD rats were randomly divided into PAN model group and normal control group.
PAN was induced by a single intravenous injection of 100 mg/kg puromycin aminonucleoside. Serum creatinine and 24-hour
urinary protein were measured on days 3, 7, and 14 after the injection, and renal pathologies were assessed with optical and
immune transmission electron microscopy. The expression of RANK and RANKL in the kidneys was examined using reverse
transcription-ploymerase chain reaction (RT-PCR) and Western blotting. Results The PAN model rats showed massive
proteinuria and elevated serum creatinine on day 3, which peaked on day 7. RANK-RANKL protein and mRNA expressions in
PAN model group was higher than those in the control group. In the PAN rats, RANK was expressed mainly on the top cell
membrane and in the cytoplasm of renal podocytes with a significantly increased expression level compared with that in the
control group. Conclusion The PAN rat model shows aberrant RANK and RANKL expressions in the podocytes, indicating
their contribution to podocyte injury in PAN.