Objective: To investigate the effect of different doses of dexamethasone (DEX) on sepsis induced acute kidney injury (AKI).
Methods: One hundred and thirty healthy male Kunming mice were randomly divided into sham group, sepsis group, physiological-dose DEX group (0.12 mg/kg), stress-dose DEX group (1.2 mg/kg), and high-dose DEX group (12 mg/kg). The sepsis model was reproduced by cecal ligation and puncture (CLP) method. Histopathological changes in the kidney were observed at 24 hours and 48 hours after CLP. The expressions of glucocorticoid receptor-α (GR-α) in the kidney were detected by immunohistochemistry. The levels of GR-α mRNA and nuclear factor-ΚB (NF-ΚB) mRNA were determined by real-time polymerase chain reaction (PCR). The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the plasma were measured by enzyme linked immunosorbent assay (ELISA).
Results: Compared with sham group mice, sepsis mice showed serious impairment in renal tubules. The mRNA and protein expression of GR-α were decreased, and NF-ΚB mRNA, plasma TNF-α and IL-1β were elevated. Compared with sepsis group, the histopathological changes in the kidney were mitigated with different levels in groups treated with different doses of DEX. GR-α protein and mRNA were up-regulated, NF-ΚB mRNA and plasma TNF-α, IL-1β were down-regulated obviously. The best effect could be seen in physiological DEX group [AKI score: 24 hours 1.480±0.334 vs. 3.040±0.517, 48 hours 1.840±0.167 vs. 3.400±0.400; GR-α protein (A value): 24 hours 0.102±0.009 vs. 0.088±0.005, 48 hours 0.103±0.008 vs. 0.085±0.006; GR-α mRNA: 24 hours 0.0400(0.0300, 0.0400) vs. 0.0100(0.0093, 0.0100), 48 hours 0.0350(0.0300, 0.0475) vs. 0.0100(0.0010, 0.0138); NF-ΚB mRNA: 24 hours 0.009±0.001 vs. 0.012±0.000,48 hours 0.011±0.000 vs. 0.013±0.001; TNF-α: 24 hours 105.84±3.84 ng/L vs. 135.52±4.49 ng/L, 48 hours 111.35±3.67 ng/L vs. 141.22±4.46 ng/L; IL-1β: 24 hours 45.71±2.93 ng/L vs. 64. 12±3.62 ng/L, 48 hours 57.04±3.04 ng/L vs. 74.87±3.67 ng/L; P<0.05 or P<0.01].
Conclusions: DEX given in physiological-dose could increase renal GR-α level and alleviate the sepsis induced kidney injury. The protective effect was much better than that of high dose DEX.