Matrine ameliorates adriamycin-induced nephropathy in rats by enhancing renal function and modulating Th17/Treg balance

摘要

Matrine (MAT) is an active alkaloid extracted from Radix Sophora flavescens. The present study was to investigate whether MAT could effectively treat Adriamycin-induced nephropathy (AIN). AIN was induced in rats using a single injection of Adriamycin (ADR). Renal interleukin-6 (IL-6), IL-10, IL-17 and transforming growth factor-beta (TGF-beta) levels, and the expression of forkhead box protein 3 (Foxp3) and retinoid-related orphan nuclear receptor gamma t (Ror gamma t) was measured. AIN rats developed severe albuminuria, hypoalbuminaemia, hyperlipidaemia and podocyte injury. Daily administration of MAT (100 mg/kg or 200 mg/kg) significantly prevented ADR-induced podocyte injury, decreased AIN symptoms and improved renal pathology manifestations. Of note, treatment with MAT (100 mg/kg) plus prednisone (Pre, 5 mg/kg) had equivalent efficacy to that of Pre alone (10 mg/kg). Additional findings showed that ADR triggered a disordered cytokine network and abnormal expression of Foxp3 and Ror gamma t in rats, as reflected by increased levels of IL-6, IL-10, TGF-beta, Ror gamma t and decreased levels of IL-10 and Foxp3. Interestingly, MAT weakened the disordered cytokine network and normalized the expression of Foxp3 and Ror gamma t. In addition, a significant negative correlation was observed between the values of Foxp3/Ror gamma t and renal pathology scores. Finally, MAT normalized regulatory T cells (Treg)/T-helperl7 cells (Th17) ratio in peripheral blood mononuclear cells of AIN rats. These data indicate MAT prevents AIN through the modification of disordered plasma lipids and recovery of renal function, and this bioactivity is at least partly attributed to the suppression of renal inflammation and the regulation of the Treg/Th17 imbalance. (C) 2016 Elsevier B.V. All rights reserved.