miR-124在FSGS小鼠中异常表达的研究

Abnormal Expression of miR-124 in a Mouse Model of Focal Segmental Glomerulosclerosis

目的探究miR-124在阿霉素(Adriamycin,ADR)诱导的局灶节段性肾小球硬化(focal seg-mental glomerulosclerosis,FSGS)小鼠模型中的表达,为阐明miR-124异常表达导致FSGS的发病机制奠定基础.方法将BALB/c小鼠随机分为对照组和实验组,一次性尾静脉注射ADR 10.5 mg/kg,28 d后取血尿及肾组织,利用ELISA法检测尿蛋白,血清肌酐;通过苏木精-伊红染色法(HE)和Masson三色染色观察肾组织形态变化;RT-PCR检测miR-124的表达水平;Western印迹检测synaptopodin蛋白的表达水平.结果实验组尿蛋白和血肌酐/体重比值水平升高(P<0.05);HE和Masson染色显示肾组织出现FSGS病理变化;miR-124表达明显上调(P<0.05)且synaptopodin蛋白表达降低(P<0.05).结论在FSGS小鼠模型中,miR-124异常高表达,synaptopodin蛋白表达下调,提示miR-124可能参与FSGS疾病中足细胞损伤的发病过程.

Objective To examine the expression of miR-124 in a mouse model of focal segmental glomerulosclerosis(FSGS)induced by adriamycin(ADR)in order to clarify the role,of miR-124 in the pathogenesis of FSGS.Methods BALB/c mice were randomly divided into control group and experimental group.Serum,urine and kidney tissues were collected 28 days after injection of ADR(10.5 mg/kg)via the tail vain.Urine protein and serum creatinine were detected by ELISA.HE and MASSON staining were performed to observe the changes of renal tissues in mice.In addition,RT-PCR was used to detect the expression level of miR-124 and Western blotting to detect the protein expression of synaptopodin.Results The level of urine protein and the blood creatinine/weight ratio were significantly increased in the experimental group(P<0.05).HE and Masson staining showed pathological changes of FSGS in kidney fissues.The expression of miR-124 was significantly up-regulated(P<0.05)and the expression,of synaptopodin protein decreased(P<0.05).1 Conclusion In the FSGS mouse model,miR-124 is abnormally over-expressed,and the expression of synaptopodin protein is down-regulated,which suggest that miR-124 may be involved in the pathogenesis of podocyte damage in FSGS disease.