Abstract
Backgrounds: The present study aimed to investigate the effects of Lectin-like Oxidized Low Density lipoprotein receptor-1 (LOX-1) as well as the interaction of LOX-1 and p38MAPK pathway in early diabetic nephropathy (DN). Methods: 30 male rats were divided into 3 groups: normal control (NC), diabetes mellitus (DM) and SB203580 (p38MAPK inhibitor) treatment (SB203580) groups. Diabetic rats were induced by Streptozotocin-injection. After the onset of diabetes, rats in SB203580 group were administrated by SB203580. Six weeks afterwards, blood glucose (BG) and serum oxLDL was evaluated. Renal function markers such as serum creatinine (sCr), blood urea nitrogen (BUN), creatinine clearance rate (cCr) and urinary albumin excretion rate (UAER) were measured. Meantime, renal glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were examined as parameters of oxidative stress. The levels of phosphorylated-p38 MAPK (p-p38MAPK) in renal cortex were evaluated by western blot and immunohistochemistry, the renal expression levels of LOX-1 protein and mRNA also were detected by western blot or real-time PCR. Results: Compared to NC group, the levels of BG, oxLDL, BUN, sCr, cCr and UAER were increased in DM group, while the activities of renal GSH-Px and SOD were significantly decreased. Meanwhile, LOX-1 expression- and p-p38MAPK levels were also upregulated in diabetic rats. However, the inactivation of p38 MAPK alleviated the upregulation of LOX-1 expression induced by diabetes. Meantime, all the parameters to evaluate renal injury were significantly attenuated by the administration of SB203580. Conclusions: The upregulation of LOX-1 by p38MAPK are important to the pathogenesis of DN.