The effect of low-dose hydrocortisone on the expression of glucocorticoid receptor alpha of the septic kidney and its protective effect on kidney in rat

Abstract

To investigate the protective effect and mechanism of low dose glucocorticoid(GC) on sepsis induced acute kidney injury(AKI) in rat. Eighty healthy Wistar male rats were randomly divided into sham group (n=10), AKI model group (AKI group, n=35)and hydrocortisone treatment group(HC group, n=35),according to random digital table. Septic AKI model was reproduced using cecal ligation and puncture (CLP). After the procedure hydrocortisone 6 mg/kg was injected via sublingual vein in HC group. At 24 hours after the procedure, blood was obtained and the animals were sacrificed in all groups. Pathological changes in the kidney were observed with hematoxylin eosin (HE) staining. The expressions of glucocorticoid receptor alpha (GR-α) and nuclear transcription factor-ΚB (NF-ΚB) in the kidney were assessed by immunohistochemistry. The levels of tumor necrosis factor alpha (TNF-α) and interleukins (IL-1β, IL-6,IL-10) in the plasma were determined by enzyme-linked immunosorbent assay(ELISA). ¹ The difference in survival rates in AKI group and HC group showed no statistical significance (42.8% vs. 48.6%,P>0.05). ² Renal tubular epithelial cells were swollen and exfoliated, with loss and vacuolation of tubular brush border under light microscope in AKI group. Pathological changes in renal tubules in HC group were alleviated. ³ Compared with AKI group, the expression of GR-α was increased [absorbance (A) value: 0.35 ± 0.05 vs. 0.25 ± 0.05,P<0.01] and the expression of NF-ΚB was decreased in HC group (A value: 0.23 ± 0.04 vs.0.34 ± 0.04,P<0.01). Compared with AKI group, the levels of TNF-α, IL-1β, IL-6 were lowered [TNF-α (ng/L): 94.25 ± 7.96 vs. 118.24 ± 6.63; IL-1β (ng/L): 19.14 ± 1.99 vs. 28.91 ± 6.81; IL-6 (ng/L): 66.32 ± 1.99 vs. 85.70 ± 11.54; all P <0.01] and the level of IL-10 (ng/L) was elevated (98.33 ± 6.68 vs. 88.59 ± 7.34,P<0.01) in HC group. A low dose of hydrocortisone can inhibit the activity of NF-ΚB, possibly by means of increasing the expression of renal GR-α in septic rats. Accordingly it reduces the production of pro-inflammatory factors which participate in sepsis. So it effectively inhibits inflammation in sepsis and protects the kidney in septic rats.