Abstract:

Objective To investigate the effects of Rapamycin on nephropathy and expression of vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR) of glomeruli in puromycin amino nuclear glucoside (PAN) nephritic mice models. Methods Twenty-four BALB/c mice were randomly divided into PAN group (model establishment by single injection of PAN via tail vein, n=8), Rapamycin intervention group (model establishment by single injection of PAN via tail vein+Rapamycin intervention, n=8) and control group (single injection of PBS via tail vein, n=8). Twenty-four-hour urine was obtained from each group, and urinary protein excretion was determined by BCA protein assay. Mice were sacrificed 10 days after model establishment, and renal tissue samples were prepared. The structural changes of foot process of glomeruli in each group was observed by transmission electron microscope, and the expression of VEGF, VEGFR1 and VEGFR2 mRNA and VEGF and VEGFR2 protein was detected by Real-time PCR, Western blotting and immunohistochemistry. Results There were significant differences in 24-h urinary protein excretion among groups (P<0.05), with PAN group>Rapamycin intervention group>control group. Foot process infusion in glomeruli was observed by electron microscopy. The expression of VEGF, VEGFR1 and VEGFR2 mRNA and protein in PAN group was the highest, and that in control group was the lowest, with significant differences among groups (P<0.05). The expression of VEGF, VEGFR1 and VEGFR2 mRNA and protein was significantly correlated with 24-h urinary protein excretion in each group (P<0.05). Conclusion Rapamycin can reduce the proteinuria of PAN nephritic mice, and the mechanism may be related to the down-regulation of expression of VEGF and VEGFR of glomeruli.

Key words: puromycin aminonucleoside nephrosis, vascular endothelial growth factor, vascular endothelial cell growth factor receptor, proteinuria, rapamycin, mouse