E-钙粘素在大鼠阿霉素肾病模型中的表达及其意义

The significance of expression of E-cadherin in rat models with adriamycin-induced nephropathy

目的动态观察E-钙粘素(E-cadherin)在大鼠阿霉素肾病模型中肾小球内的表达,探讨其变化在肾小球疾病中的作用。方法采用大鼠尾静脉单剂量注射阿霉素(浓度2 mg/ml,剂量7.5 mg/kg)建立阿霉素肾病模型,生化检测白蛋白变化,尿液检测24 h尿蛋白定量,光镜下观察肾小球形态学改变,免疫组化检测肾组织E-cadherin和纤维连接蛋白(FN)的表达。结果阿霉素肾病组大鼠肾脏肾小球形态于第4周时出现微小病变,第8周时为局灶阶段性硬化;并且肾病组大鼠均出现大量蛋白尿、低蛋白血症,肾病组与对照组相比,差异具有显著性(P<0.01);E-cadherin在肾小球足细胞的表达随着肾小球病变的加重而逐渐减少;FN在肾小球内的表达随着肾小球病变的加重而逐渐增加;E-cadherin和FN在肾组织内的表达呈负相关(r=0.926,P<0.001)。结论阿霉素肾病组大鼠肾小球E-cadherin表达减少和FN表达增加在不同阶段表达的变化可能参与了肾小球硬化的发生发展过程。

Objective To study the significance of expression of E-cadherin in glomeruli of rat models with adriamycin-induced nephropathy,and to explore its role in pathogenesis of glomerular diseases.Methods The rat model of nephropathy was established by injection of adriamycin（with concentration of 2mg/ml and dosage of 7.5 mg/kg） through their tail vein.The serum levels of albumin were determined by biochemical method,and the quantitative determination of protein was examined with 24 hours urine.The expressions of E-cadherin and fibronectin（FN） in glomeruli were detected by immunohistochemical method.Results The rat model with ADR nephropathy was successfully established.In comparison with control group,minimal pathological changes were observed in rats with adriamycin-induced nephropathy at fourth week,and lesions of focal segmental glomerulosclerosis were observed at eighth week.In comparison with control group,there was significant difference in albuminuria and hypoalbuminemia between nephropathy group and control group（P〈0.01）.The expression of E-cadherin in glomerular podocytes was gradually decreased with the aggravation of local lesions in glomeruli,and it will prevent the development of glomerulosclerosis.The expression of FN in glomeruli was gradually increased,and it will promote the development of glomerulosclerosis.The expressions of E-cadherin and FN in glomeruli showed significantly negative correlation（r=0.926,P0.001）.Conclusion The expression of E-cadherin is reduced and FN is increased in different stages of rat models with adriamycin-induced nephropathy,and glomeruli may be involved in the process of development of glomerular sclerosis.