O-ClcNAc修饰在谷氨酰胺诱导内毒素休克大鼠心肌组织HSP70表达中的作用

The role of O-GlcNAc modification in glutamine-induced myocardial heat shock protein 70 expression in a rat model of endotoxic shock

目的 探讨O位-N-乙酰葡糖胺（O-GlcNAc）修饰在谷氨酰胺诱导内毒素休克大鼠心肌组织热休克蛋白70（HSP70）表达中的作用.方法 健康雄性SD大鼠32只,随机分为4组（n=8）,正常对照组（C组）仅静脉输注乳酸钠林格氏液;LPS组、G＋LPS组和A＋G＋LPS组均静脉注射LPS10 mg/kg,G＋LPS组给予LPS前1 h静脉注射谷氨酰胺0.75 g/kg,A＋G＋LPS组给予LPS前1h依次静脉注射谷氨酰胺0.75 g/kg和O-位-N-乙酰葡萄糖胺糖基转移酶抑制剂四氧嘧啶50 mg/kg.注射LPS后6 h处死大鼠,取心肌组织,测定O-GlcNAc和HSP70的表达水平.结果 与C比较,其他各组心肌O-GlcNAc和HSP70的表达水平均上调（P＜0.05）;与LPS组比较,G＋LPS组心肌O-GlcNAc和HSP70的表达水平上调（P＜0.05）;与G＋LPS组比较,A＋G＋LPS组心肌O-GlcNAc和HSP70的表达水平下调（P＜0.05）.结论 O-GlcNAc修饰参与了谷氨酰胺诱导内毒素休克大鼠心肌HSP70表达上调.

Objective To investigate the role of O-linked N-acetylglutamine （O-GlcNAc） modification in glutamine-induced myocardial heat shock protein （HSP70） expression in a rat model of endotoxic shock. Methods Thirty-two 8 weeks old male SD rats weighing 250-300 g were randomly divided into 4 groups （n = 8 each）：group Ⅰ control （group C）; group Ⅱ LPS; group Ⅲ G＋ LPS and group glutamine ＋ LPS （group A ＋ G ＋ LPS）. Endotoxic shock was induced by iv administration of LPS 10 mg/kg in group Ⅱ , Ⅲ and Ⅳ.Glutamine 0.75 g/kg was administered iv at 1 h before iv LPS in group Ⅲ and Ⅳ . Alloxan （an inhibitor ofO-linked N-acetylglucosamine transferase） 50 mg/kg was administered iv together with glutamine at 1 h before LPS in group Ⅳ. The animals were sacrificed at 6 h after iv LPS administration. Their hearts were removed for determination of the expression of O-GlcNAc and HSP70 in myocardium. Results Intravenous LPS significantly up-regulated the expression of O-GlcNAc and HSP70. Glutamine pretreatment further increased the expression of O-GlcNAc and HSP70. The glutamine pretreatment induced increase in O-GlcNAc and HSP70 expression was abolished by concomitant administration of alloxan. Conclusion O-GlcNAc modification may be involved in glutamine-induced myocardial HSP70 expression in endotoxic shock.