The role of sirolimus in proteinuria in diabetic nephropathy rats

OBJECTIVE(S): The aim of this study was to observe the impact of sirolimus on proteinuria in streptozotocin (STZ) induced diabetic rats. MATERIALS AND METHODS: Rats were given a single injection of STZ to induce diabetic rat model. Rats’ 24 hr urine was collected to test, urinary and the kidney tissues were harvested at the 8(th) and 20(th) weeks, respectively. Podocyte morphological changes were examined by electron microscopy and the ZO-1, podocin expressions in kidneys were detected by immunohistochemistry; the protein levels of Raptor and pS6 were measured by Western blot assay. RESULTS: In the early stage of diabetic nephropathy (DN), sirolimus reduced the proteinuria significantly (P<0.05); but in the advanced stage of DN, sirolimus worsened proteinuria (P<0.05). Electron microscopy test suggested that sirolimus could reduce the injury of podocyte at the early DN, but increased the injury at the late DN podocyte. Immunohistochemistry results indicated that sirolimus increased the expressions of podocin and ZO-1 at the early DN (P<0.05), but reduced the expressions of ZO-1 and podocin (P<0.05) at the advanced DN. In the different periods of DN, the expression levels of Raptor and pS6 in sirolimus-treated groups were significantly lower than in the DN control groups (P<0.05). CONCLUSION: Sirolimus can reduce proteinuria and alleviate the early DN podocyte injury in diabetic rat model by inhibiting the activity of mTORC1; but in the advanced stage of DN, sirolimus can increase podocyte injury and urine protein level.