糖尿病肾病早期白蛋白尿与Megalin的表达变化

目的:通过链脲佐菌素(STZ)诱导糖尿病肾病大鼠Megalin的表达变化,了解糖尿病肾病时肾小管重吸收白蛋白的能力与Megalin的关系.方法:将SD大鼠分为正常对照组(N组)和糖尿病肾病组(DN组).DN组以55 mg/kg体重的剂量一次性腹腔注射1%STZ,N组一次性腹腔注射柠檬酸缓冲液.在实验的2、4、6周分别处死两组的5只大鼠,并测量大鼠的血糖、24 h尿量、24 h尿白蛋白量、24 h尿肌酐浓度、血清肌酐和尿素氮、体重和肾脏重量,计算肌酐清除率和肾脏肥大指数,应用免疫组化和RT-PCR技术观察各组大鼠2、4、6周的肾小管Megalin表达.结果:第2周DN组的Megalin表达水平与N组相比有显著下降(P＜0.05),与第6周比较DN组Megalin表达逐渐降低,且有统计学差异(P＜0.05).结论:STZ腹腔注射所致大鼠糖尿病肾病的24 h白蛋白尿增加与肾小管近端的Megalin表达呈显著负相关关系.Megalin表达的降低不是一过性,也不能自行恢复,不加干预会随着病程延长而逐渐加重.

The Relationship Between the Expression of Megalin and Microabluminuria in Diabetic Nephropathy

Objective:To study the expression of the megalin in the renal tubules of STZ-induced diabetic nephropathy rats and its relation with albuminuria.Methods:Sprague-Dalwley (SD) rats were randomly divided into two groups: normal control and diabetic nephropathy. Diabetes was induced by intraperitoneal injection of STZ. Five rats in each groups were sacrificed at week 2,4, and 6 respectively. Blood glucose, body weight, kidney weight, 24-hour urinary protein excretion, 24-hour urine volume,24-hour urine creatinine concentration, serum creatinine and urea nitrogen were examined at week 2,4,and 6 respectively. Creatinine clearance and renal hypertrophy index were calculated. The renal expression of megalin were determined by immunohistochemistry and RT-PCR at week 2, 4 and 6 respectively.Results:Megalin expression was significantly inhibited in the proximal convoluted tubules of diabetic rats compared to the controls at 2 week. Inhibition of megalin expression at 6 week was more significant than that at 2 or 4 week.Conclusion:The expression of megalin dramatically decreased in the early stage of diabetic nephropathy.Inhibition of expression of megalin can not be recovered without treating.The expression of megalin was negatively correlated with albuminuria.