RT Journal Article
SR Electronic
T1 Metformin meliorated glucocorticoid resistance through activating AMPK in septic rat
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA2269
DO 10.1183/13993003.congress-2019.PA2269
VO 54
IS suppl 63
A1 Huoyan Liang
A1 Xianfei Ding
A1 Tongwen Sun
A1 Junyi Sun
YR 2019
UL http://erj.ersjournals.com/content/54/suppl_63/PA2269.abstract
AB Background: Acquired glucocorticoid resistance (GCR) frequently complicates the treatment of sepsis. It leads to an exaggerated pro-inflammatory response and has been related to decrease expression profiles of the glucocorticoid receptor (GR). This study aimed to test the hypothesis that metformin may reverse the GR level decreased by inflammatory transcription factor κB via activating adenosine monophosphate-activated protein kinase (AMPK), thereby meliorated GCR in septic rat.Methods: A total of 60 adult male Sprague-Dawley rats were randomly divided into 3 groups: a sham-operated (Sham) group, a sepsis-induced by cecal ligation and puncture (CLP) group, an MET group (which underwent CLP followed by peritoneal injection of 100mg/kg metformin 2 h after surgery). The rats were sacrificed at 24 h after the sham or CLP procedures and harvested the blood and liver samples.Results: The mortality had no difference between CLP and MET groups. Compared with Sham and CLP groups, the expression of AMPK-α significantly increased in MET group. The serum lactate levels were the lowest in the Sham group and highest in CLP group, metformin can decrease the lactate levels. In the CLP group, the expression of NF-κB were higher in nuclear than that in the Sham and MET groups. The expression of nuclear GR in the CLP group was lower than that in the MET and Sham groups.Conclusions: Therapeutically administered metformin activated AMPK, which regulates GR expression by downregulating NF-κB (p65). This mechanism most likely ameliorates glucocorticoid resistance by reversing the nuclear shift of GR.Keywords: metformin; AMPK; glucocorticoid resistance; sepsisFootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA2269.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).