Effect of Combination Therapy with Angiotensin Receptor Blocker and 1,25-Dihydroxyvitamin D_3 in Type 2 Diabetic Nephropathy in KK-A~y/Ta Mice

摘要

Background: Although angiotensin II type 1 receptor block-ers (ARB) have beneficial effects in patients with diabetic nephropathy, they may induce a compensatory increase in re-nin. Renin exhibits prof ibrotic actions independent of angiotensin II, which is regulated by extracellular signal-regulated kinase 1 and 2 (ERK1/2). Calcitriol (1,25(OH)_2D_3) is a negative inhibitor of the renin-angiotensin system and the present study examined the effects of combination therapy with an ARB and 1,25(OH)_2D_3 on diabetic nephropathy in KK-AVTa mice. Methods: KK-AVTa mice were divided into four groups: ARB group, 1,25(OH)_2D_3 group, combination group, and control group. The urinary albumin/creatinine ratio (ACR) was measured and the renal expression of renin, p-ERK1/2 and TGF-beta1 protein determined. Results: The levels of urinary ACR in the combination group were significantly lower than those in the ARB or control group. Renal expression of renin in the ARB group was significantly increased compared with the control group but was significantly decreased in both the 1,25(OH)_2D_3 and combination group.