Role of protein O-linked N-acetyl-glucosamine modification in glutamine-induced improvement in vascular hyporeactivity in rats with septic shock / 中华麻醉学杂志

ABSTRACT

Objective To investigate the role of protein O-linked N-acetyl-glucosamine (O-GlcNAc) modification in glutamine-induced improvement in the vascular hyporeactivity in rats with septic shock.Methods Thirty-two adult male Sprague-Dawley rats,aged 2-3 months,weighing 250-300 g,were randomly divided into 4 groups (n =8 each)sham operation group (S group); septic shock group (C group); glutamine group (G group) ; alloxan group (A group).Septic shock was induced by cecal ligation and puncture (CLP).In G and A groups,glutamine 0.75 g/kg was infused intravenously over 30 min at 1 h before CLP,and in addition alloxan 90 mg/kg was infused intraperitoneally in A group.Phenylephrine (PE) 0.5,1.0,2.0,and 2.5 μg/kg was injected intravenously at 20 min intervals at 6 h after CLP and the percentage increase in mean arterial pressure (MAP) was calculated.The thoracic aorta rings were isolated to perform the isolated vascular tension experiment.The concentration-response curve of PE was obtained in tension experiments,and the PE maximum efficacy (Emas) and median effective dose ( EC50 ) were calculated.The expression of O-GlcNAc modification and iNOS content in the thoracic aorta were detected in all groups.Blood samples were taken to determine the serum concentration of NO.Results Compared with S group,the percentage increase in MAP and Emax were significantly decreased,while the EC50,serum concentration of NO,and expression of O-GlcNAc modification and iNOS content in thoracic aorta were significantly increased in C,G and A groups ( P ＜ 0.05).Compared with C group,the expression of O-GlcNAc modification in the thoracic aorta was significantly increased,and EC50 was significantly decreased in G group,and the percentage increase in MAP and Emax were significantly increased,while the serum concentration of NO,and content of iNOS in the thoracic aorta were significantly decreased in G and A groups ( P ＜ 0.05).Compared with G group,the EC50,serum concentration of NO,and content of iNOS in the thoracic aorta were significantly increased,while the percentage increase in MAP,Emax and expression of O-GlcNAc modification in the thoracic aorta were significantly decreased ( P ＜ 0.05 ).Conclusion Glutamine improves the vascular hyporeactivity through increasing the level of protein O-GlcNAc modification in rats with septic shock.