title: 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 3 days following catheterization. The rats were randomly divided into five groups. All groups were infused with 2 ml of either etomidate or 5‰ dimethyl sulfoxide (DMSO) at 1 ml/h for 2 h from 6 h post‑surgery. The sham group received abdominal sham surgery and infusion with DMSO; the CLP control group received infusion with DMSO. Treatment group A received infusion with 2 mg/kg etomidate; group B received 0.6 mg/kg etomidate following CLP and an infusion of 2 mg/kg etomidate. Group C received 0.6 mg/kg etomidate 24 h 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.
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Ruo-Meng
authors.initials: RM
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Biology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Shen
authors.initials: S
authors.lastname: Lv
authors.affiliation: Department of Anesthesiology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Xiong
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D005045:Etomidate / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism; D018805:Sepsis / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality
chemical_list: D018686:Anesthetics, Intravenous; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D005045:Etomidate