Etomidate inhibits nuclear factor-κB through decreased expression of glucocorticoid receptor in septic rats.

Abstract

The present study aimed to investigate the effect of etomidate administered prior to or following cecal ligation and puncture (CLP) on the expression of glucocorticoid receptor (GR) and lymphocyte apoptosis in septic rats. Right jugular vein catheterization was performed on female Sprague‑Dawley rats under isoflurane anesthesia, and CLP surgery was performed to induce sepsis 3days following catheterization. The rats were randomly divided into five groups. All groups were infused with 2ml of either etomidate or 5‰ dimethyl sulfoxide (DMSO) at 1ml/h for 2h from 6h post‑surgery. The sham group received abdominal sham surgery and infusion with DMSO; the CLP control group received infusion with DMSO. Treatment groupA received infusion with 2mg/kg etomidate; group B received 0.6mg/kg etomidate following CLP and an infusion of 2mg/kg etomidate. Group C received 0.6mg/kg etomidate 24h prior to CLP and post‑surgical etomidate infusion. The 10‑day survival rates of the rats in the CLP, A, B and C groups were 60, 50, 55 and 40%, respectively. The serum mRNA expression levels of tumor necrosis factor‑α, GR and glucocorticoid‑induced leucine zipper were detected by reverse transcription‑quantitative polymerase chain reaction, the abundance of inhibitor of nuclear factor (NF)-κB‑α was measured by western blotting, and the apoptotic rates of the splenic lymphocytes were determined using flow cytometry. The results suggested that etomidate inhibited NF‑κB by decreasing the expression of GR in the septic rats. The increased apoptosis of lymphocytes induced by etomidate may lead to a poor outcome during sepsis.