目的探讨基质细胞衍生因子1(SDF-1)在IgA肾病小鼠的表达以及FTY720对SDF-1表达的影响。方法 30只BALB/c小鼠,随机分为3组,每组10只。IgA肾病模型组及FTY720治疗组均采用黏膜免疫复合物法造模,第9周起对FTY720组给予FTY720干预,另设正常对照组。收集实验第4、8、12周时尿液,检测尿红细胞及尿蛋白定量;第12周末处死动物留取肾脏,普通光镜及免疫荧光法检测肾脏病理改变,SABC法检测肾脏SDF-1蛋白的表达,实时定量PCR技术分析肾脏SDF-1 mRNA的表达差异。结果模型组小鼠自8周后开始出现蛋白尿,肾脏呈现典型的系膜增殖性改变,FTY720干预组蛋白尿及肾小球病变较轻。SDF-1蛋白在正常小鼠及经FTY720干预小鼠肾脏组织均呈低表达,但在模型鼠肾脏组织中呈强阳性表达。SDF-1mRNA在模型组小鼠肾脏组织中的表达较正常组有所增加,而在经FTY720干预的小鼠肾脏组织中的表达则较模型组明显减少。结论 SDF-1可能作为IgA肾病肾脏损伤及肾间质纤维化的一项指标存在。FTY720对IgA肾病具有良好的治疗效果,它可能通过影响SDF-1在肾脏的表达发挥治疗作用。
Objective To study the effect of FTY720 on the expression of stromal cell-derived factor-1(SDF-1)in mouse model of IgA nephropathy(IgAN).Methods A total of 30 female BALB/c mice were randomly divided into 3 groups(n=10 each group):control group,IgAN model group,and FTY720 group.The 24-hour urine protein was quantified by coomassie brilliant blue at weeks 4,8,and 12.All the mice were killed after 12 weeks,and the kidneys were sampled.The pathological changes in the kidney were observed under light microscope and detected by immunofluorescence.The levels of SDF-1 protein and mRNA in the kidney were detected by SABC immunohistochemical method and real-time reverse transcription polymerase chain reaction,respectively.Results Proteinuria and mesangial cell proliferation were observed in IgAN model group since week 8,and these pathological changes were less severe in FTY720 group.The expression level of SDF-1 protein was low in control and FTY720 groups,but strongly positive expression of SDF-1 protein was found in IgAN group.The expression of SDF-1 mRNA in IgAN model group increased,compared with control group.The expression of SDF-1 mRNA was lower in FTY720 group than in IgAN model group.Conclusion SDF-1 might be an indicator of renal injury and fibrosis of IgAN.FTY720 has a good therapeutic effect on IgAN by affecting the expression of SDF-1 in the kidney.