Relationship between expression of nephrin, podocin and ? actinin with proteinuria in puromycin aminonucleoside nephrosis rats / 中华肾脏病杂志

ABSTRACT

Objective To study the expression of nephrin, podocin and ? actinin in glomeruli in puromycin aminonucleoside (PAN) nephrosis rat,and to disclose the possible association of these molecules with the development of proteinuria and the relation among these molecules′changes. Methods PAN nephrosis rat models were established by a single intraperitoneal injection of PAN. Indirect immunofluorescence (IF) staining and real time quantitative reverse PCR were used to study the expression of nephrin, podocin and ? actinin in glomeruli of model rats at 12 hours, 1 day, 36 hours,2 days, 5 days, 10 days, 15 days and 20 days after PAN injection. Results (1)In PAN rats, the urinary protein reached the peak level (P=0 02) at the 10th day and decreased back to control level at the 20th day. (2)The IF intensity of podocin decreased significantly at the 36th hr (P=0 04), the 2nd day(P=0 03), the 5th day(P=0 04) and the 10th day(P=0 006),while at the 15th day,the intensity began to recover (P=0 007)and reached to the control level at the 20th day. The distribution of podocin showed a linear pattern along the glomerular capillary wall (GCW) in control rats and discontinuous in PAN rats. (3)The intensity of nephrin staining decreased significantly at the 5th day (P=0 002), 10th day (P=0 007) and began to recover at the 15th day (P=0 04), while still abnormal at the 20th day(P=0 02). The distribution of nephrin in control rats showed a linear pattern along the GCW whereas a discontinuous pattern in PAN rats from the first day throughout the course. (4)The intensity of ? actinin in PAN rats increased significantly at the 20th day(P=0 009) accompanied by the increase of area ratio (P=0 007). (5)The mRNA of nephrin decreased(P =0 02)at the 5th day and recover at the 10th day. Conclusions Nephrin and podocin change prior to the presence of heavy proteinuria, which suggests their causative effects to proteinuria in PAN nephrosis. The distribution changes of nephrin and podocin occurre before the decrease of their expression level and seem to be an initial trigger factor of proteinuria. The significant decrease and recovery of podocin presents earlier than those of nephrin.The proteinuria level is correlated with the expression of podocin and nephrin.