Nephrin、TGF-β1和WT1在阿霉素肾病模型肾小球中的表达及意义

目的 探讨足细胞的数量及nephrin、转化生长因子-β1(TGF-β1)蛋白在阿霉素肾病模型肾小球中的表达及意义.方法 建立阿霉素诱导的大鼠肾病模型,于不同实验时间点检测血、尿生化指标;光镜、电镜观察肾脏的组织病理学改变;免疫组化技术检测足细胞数量、nephrin、TGF-β1蛋白的表达情况.结果 该模型的肾脏病理学改变明显;1周末足细胞nephrin表达减弱(P<0.05),8周末肾小球TGF-β1表达增强(P<0.05)、足细胞数量减少(P<0.05);nephrin与24h尿蛋白定量(r=-0.83,P<0.01)、尿素氮(r=-0.68,P<0.05)、血肌酐(r=-0.71,P<0.05)呈负相关;TGF-β1与24h尿蛋白定量(r=0.45,P<0.05)、尿素氮(r=0.62,P<0.05)、血肌酐(r=0.59,P<0.05)呈正相关;足细胞数量与24h尿蛋白定量(r=-0.63,P<0.05)、尿素氮(r=-0.72,P<0.05)、血肌酐(r=-0.76,P<0.05)呈负相关;足细胞数量与nephrin呈正相关(r=0.78,P<0.01),与TGF-β1呈负相关(r=-0.64,P<0.05). 结论经改良间隔2周两次尾静脉注射阿霉素(4mg/kg)可以成功复制阿霉素肾病急性和慢性模型;阿霉素肾病蛋白尿的发生和进展与nephrin表达异常密切相关;TGF-β1加重了足细胞数量减少启动的局灶节段性肾小球硬化.

Expression of nephrin, TGF-β1 and WT1 in adriamycin-induced-nephropathy rat model and its significance

Objective To investigate podocyte number, the expression of nephrin and transforming growth factor-β1(TGF-β1) in adriamycin-induced-nephropathy rat model and its significance. Methods The rat adriamycin nephrosis model was constructed to detect blood and urine biochemical indicators and observe the pathological changes of renal tissues by light microscope and electron microscope. The expression levels of nephrin and TGF-β1 as well as the podocyte number were examined at different time points by immunohistochemistry. Results The pathological changes of the renal tissues were obvious. Nephrin presented a weak signal at the end of the first week (P<0.05). TGF-β1 started to increase (P<0.05) while the podocyte number started to decrease at the end of the eighth week (P<0.05). Expression of nephrin was negatively correlated with the P<0.05) and serum creatinine (r=-0.71, P<0.05). Expression of TGF-β1 was blood urea nitrogen (r=0.62, P<0.05) and serum creatinine (r=0.59, urinary protein (r=-0.63, P<0.05), blood urea nitrogen (r=-0.72, P<0.05) and serum creatinine (r=-0.76, P<0.05); it was positively correlated with nephrin (r=0.78, P<0.01) but negatively correlated with TGF-β1 (r=-0.64, P<0.05). Conclusion The acute and chronic adriamycin nephrosis models were twice every two weeks. The genesis and development of proteinuria are closely related to the abnormal expression of nephrin. Focal segmental glomerulosclerosis occurs when the podocyte number decreases and TGF-β1 accelerates it.