Cubilin在糖尿病肾病大鼠模型的表达变化

目的 观察链脲佐菌素（STZ）糖尿病肾病大鼠模型肾小管Cubilin的表达变化，及其与白蛋白尿的关系，探讨糖尿病肾病早期的肾小管功能障碍可能的机制。方法 糖尿病肾病大鼠（DN）模型采用STZ一次性腹腔注射制备，正常组（N）大鼠注射等量生理盐水。于实验2、4、6周分别处死两组大鼠并测量相关血尿生化指标，应用免疫组化和RT—PCR技术观察各组大鼠的肾小管Cubilin蛋白和mRNA表达水平。结果 与正常组相比，DN组大鼠肾小管的Cubilin蛋白和mRNA表达水平在第2周即明显下降（P〈0．05），并随时间推移继续降低，各时间点差异有统计学意义（P〈0．05），Cubilin mRNA的表达水平与白蛋白尿呈显著负相关（r=-0．815，P〈0．01）。结论 肾小管Cubilin表达的下降可能部分参与了糖尿病肾病早期微量白蛋白尿的发生，Cubilin可望作为糖尿病肾病肾小管受损的早期标志之一。

Expression Level of Cubilin in the Rat Model of Diabetic Nephropathy

Objective To observe the expression level of Cubilin in the renal tubules of rats with STZ-induced diabetic nephropathy, to assess its correlation with 24 hours' albuminuria, and to investigate the mechanisms of tubular dysfunction at the early stage of diabetic nephropathy. Methods Diabetic nephropathy was induced in Sprague-Dalwley rats by intraperitoneal injection of STZ, while the rats of normal group were injected with normal saline. Biochemical indices of blood and urine specimens were observed in both groups at weeks 2, 4 and 6 respectively. The renal expression levels of Cubilin in the two groups were determined by immunohistochemistry and RT-PCR. Results The expression level of Cubilin in the diabetic nephropathy group was significantly decreased at week 2 after operation (P<0.05), and it continued to decrease from week 2 to week 6. Also there was significant difference between each two time-points (P<0.05), and the Cubilin expression level was negatively correlated with albuminuria (P<0.01). Conclusion The decreased expression level of Cubilin in early-stage diabetic nephropathy rats may partly contribute to the development of microalbuminuria. Cubilin can be regarded as one of the early markers when tubular dysfunction develops in the case of diabetic nephropathy.