AB176. Icariside II ameliorates diabetic nephropathy in streptozotocin-induced diabetic rats

Abstract

ObjectiveTo investigate the therapeutic effects and potential mechanisms of icariside II (ICA II) on improving diabetic nephropathy (DN) in streptozotocin (STZ) induced type I diabetic rats.MethodsNewborn male Sprague-Dawley rats were labeled with thymidine analog 5-ethynyl-2-deoxyuridine (EdU) for tracking endogenous label retaining progenitor cells (LRCs). At age of 8 weeks, 16 rats were chosen as normal control (NC) and 32 rats were induced for diabetes with STZ, 8 weeks later, diabetic rats were equally randomized into diabetic group (DM) and ICA II therapy group (DM + ICA II) that were treated with vehicle or ICA II (5 mg/kg/day) for 8 weeks, respectively. Then blood creatinine (Cr), 24-h urine protein, blood urea nitrogen (BUN), and HbA1c were measured, as well as the expression of von Willebrand Factor (vWF), MDA, TGF-β/Smad/CTGF signaling, Ki67, and EdU + LRCs in renal tissues.ResultsIncreased levels of Cr, 24-h urine protein, and BUN, and remarkably decreased proportion of normal glomeruli and increased proportions of I, IIa, IIb, and III glomeruli were observed in diabetic rats, while ICA II could reverse these changes. Interestingly, ICA II could significantly down-regulate the levels of MDA and TGF-β/Smad/CTGF signaling and increase the expression of vWF, Ki67, and EdU + LRCs in the kidney.ConclusionsICA II treatment could ameliorate DN in STZ-induced diabetic rats by increasing endothelial cell contents, down-regulating TGF-β/Smad/CTGF signaling pathway and oxidative stress level, and promoting cell proliferation. These beneficial effects appear to be mediated by its antioxidant capacity and recruitment of endogenous EdU + progenitor cells into the kidney tissue.