Effects of prednisone acetate on renal function, renal inflammation and AMPK/SIRT1 signaling pathway in diabetic nephropathy rats

Abstract

Objective To explore the effect of prednisone acetate on renal function, renal inflammatory response and AMP-activated protein kinase (AMPK)/silent information regulator 1 (SIRT1) signaling pathway in diabetic nephropathy (DN) rats. Methods Twelve rats were randomly selected as the control group, and the remaining rats were given high-sugar and high-fat diet supplemented with intraperitoneal injection of streptozotocin (STZ) to construct a DN rat model. The successful model rats were randomly divided into model group, prednisone acetate low (6.25 mg/kg), high (12.5 mg/kg) dose groups, prednisone acetate + CC group (prednisone acetate 12.5 mg/kg+AMPK inhibitor compound C 0.2 mg/kg), with 12 animals in each group. Each group was given corresponding treatment, once a day for 4 weeks. The general state of rats was observed, and the fasting blood glucose (FBG), 24-hour urine microalbumin (U-mAlb), blood creatinine (SCr), blood urea nitrogen (BUN), serum interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected; the pathological changes of renal tissue were observed with hematoxylin eosin (HE) staining and periodate schiff (PAS) staining; The expression of proteins related to the renal tissue AMPK/SIRT1 signaling pathway was detected with Western blot. Results Prednisone acetate can improve the general state of DN rats, reduce FBG, 24 h U-mAlb, serum SCr, BUN, IL-1β, IL-6 and TNF-α levels, and renal tissue acetylation nuclear factor-κB p65 (ac-NF-κB p65)/NF-κB p65 and monocyte chemotactic protein-1 (MCP-1) protein expression (P＜0.05), increase phosphorylated AMPK(p-AMPK)/AMPK and SIRT1 protein expression (P＜0.05), improve kidney disease; compound C could significantly weaken the protective effect of prednisone acetate on DN rats. Conclusions Prednisone acetate can reduce renal inflammatory response and protect renal function in DN rats. Its mechanism may be related to the activation of AMPK/SIRT1 pathway to inhibit the activation of NF-κB.

Keywords

• prednisone acetate|diabetic nephropathy|inflammatory reaction|amp-activated protein kinase/silent information regulator 1 signaling pathway(ampk/sirt1)