Abstract：Objective This paper aims at studying the effects of alphacalcidol (αD 3) on Wilms' tumor 1 gene (WT 1) expression of renal tissues and on proteinuria in rats with nephrotic syndrome so as to understand the mechanism of proteinuria occurrence. Methods One hundred and twenty SD rats were randomly assigned into five groups: a Control group, a Nephropathy group, a Prednisone-treated nephropathy group (Prednisone group), a αD 3-treated nephropathy group (αD 3 group) and a Prednisone and αD 3-treated group (Combination group). Nephrotic syndrome rat models were established by an injection of adriamycin via the tail vein. The Control group received an injection of 0.1 ml normal saline. After 2 weeks of injections, different treatments were given for the 5 groups daily for 4 weeks. The Prednisone group was administered prednisone daily (12 mg/kg); the αD 3 group was administered αD 3 daily ( 0.03 μg/kg); and the Combination group was administered prednisone (12 mg/kg) and αD 3 ( 0.03 μg/kg) daily. The Control group and the Nephropathy group were given distilled water with the same volume as the 3 treatment groups. Every 2 weeks specimens of the urine of 8 rats in each group were collected for 24 hrs in order to detect the 24-hr urinary protein content, and then the rats were sacrificed for histological study. Immunofluorescence was used to detect the WT 1 expression of renal tissues. Results By the 2nd week, the 24-hr urinary protein contents of the Nephropathy group, the Prednisone group, the αD 3 group and the Combination group were significantly higher than that of the Control group (P< 0.01). By the 4th and 6th weeks, the 24-hr urinary protein contents increased in the Nephropathy group, while those of the Prednisone group, the αD 3 group and the Combination group gradually decreased compared with those of the 2nd week. There were significant differences between the Nephropathy group and the 3 treated-nephropathy groups (P< 0.01). By the 2nd week, the WT 1 expressions of the Nephropathy group, the Prednisone group, the αD 3 group and the Combination group were significantly lower that of the Control group (P< 0.01), while the pathologic scores of the 4 nephropathy groups were significantly higher that of the Control group (P< 0.01). By the 4th and 6th weeks, the WT 1 expression in the Nephropathy group decreased, while those of the 3 treated-nephropathy groups elevated compared with those of the 2nd week. Significant differences were found between the Nephropathy group and the 3 treated- nephropathy groups. The WT 1 expression was negatively correlated to the 24-hr urinary protein content (P< 0.01). By the 4th week, the pathologic scores of the Prednisone group, the αD 3 group and the Combination group rose compared with those of the 2nd week, but they decreased by the 6th week. The pathologic scores of the αD 3 group by the 4th and 6th weeks were lower than that of the Nephropathy group (P< 0.01). Conclusions αD 3 may have protective effects against nephrotic syndrome by increasing the WT 1 expression and decreasing the drainage of proteinuria.
LIN Xiao-Qin,YI Zhu-Wen,WU Xiao-Chuan et al. Effect of alphacalcidol on Wilms'tumor 1 gene expression in rats with nephrotic syndrome induced by adriamycin[J]. CJCP, 2004, 6(3): 195-198.
