Singleton Kristen D, Serkova Natalie, Banerjee Anirban, Meng Xianzhong, Gamboni-Robertson Fabia, Wischmeyer Paul E
Department of Anesthesiology, University of Colorado Health Sciences Center, Denver, Colorado, USA.
Nutrition. 2005 Feb;21(2):214-23. doi: 10.1016/j.nut.2004.05.023.
Septic shock leads to derangement of cellular metabolism. Enhanced heat shock protein 70 (HSP-70) can preserve cellular metabolism after other forms of cellular stress. Glutamine (GLN) can enhance lung HSP-70 expression after lethal endotoxemia. However, it is unknown whether GLN can enhance HSP-70 expression and attenuate lung metabolic dysfunction after sublethal endotoxemia. Our aim was to determine whether GLN could upregulate HSP-70 and attenuate metabolic dysfunction in lung tissue after sublethal endotoxemia.
Sprague-Dawley rats were assigned to one of five groups. The first two groups were treated with Escherichia coli lipopolysaccharide (LPS; 1 mg/kg intravenously). GLN (0.75 g/kg intravenously) or balanced salt solution as a control was administered 5 min after LPS administration. The next two groups of rats were treated with quercetin (HSP-70 inhibitor; 400 mg/kg intraperitoneally) 6 h before LPS administration. The final group received no treatment. Lung tissue was harvested 24-h after LPS and analyzed with immunofluorescence and western blot for HSP-70. Tissue metabolites were quantified by 1H and 31P nuclear magnetic resonance spectroscopy.
GLN compared with balanced salt solution (BSS) administration in LPS-treated animals led to significant increases in lung HSP-70. Increased HSP-70 expression was observed in lung epithelial cells and macrophages. GLN significantly improved the ratio of adenosine triphosphate to adenosine diphosphate in the lung after LPS. Quercetin inhibited a GLN-mediated increase in lung HSP-70 and blocked a beneficial effect of GLN on the ratio of adenosine triphosphate to adenosine diphosphate after LPS.
A single dose of GLN can enhance HSP-70 in pulmonary epithelial cells and macrophages after sublethal endotoxemia. Further, GLN can attenuate endotoxin-induced lung metabolic dysfunction. GLN's beneficial effect on lung tissue after metabolic dysfunction caused by sublethal endotoxemia may be mediated in part by enhanced HSP-70.
脓毒症休克会导致细胞代谢紊乱。增强型热休克蛋白70（HSP - 70）在其他形式的细胞应激后可维持细胞代谢。谷氨酰胺（GLN）可在致死性内毒素血症后增强肺组织中HSP - 70的表达。然而，尚不清楚在亚致死性内毒素血症后GLN是否能增强HSP - 70的表达并减轻肺代谢功能障碍。我们的目的是确定GLN是否能上调亚致死性内毒素血症后肺组织中的HSP - 70并减轻代谢功能障碍。
将Sprague - Dawley大鼠分为五组。前两组静脉注射大肠杆菌脂多糖（LPS；1 mg/kg）。在注射LPS 5分钟后，分别静脉注射GLN（0.75 g/kg）或平衡盐溶液作为对照。接下来的两组大鼠在注射LPS前6小时腹腔注射槲皮素（HSP - 70抑制剂；400 mg/kg）。最后一组不进行处理。在注射LPS 24小时后采集肺组织，通过免疫荧光和蛋白质印迹法分析HSP - 70。通过1H和31P核磁共振波谱法定量组织代谢物。
与在LPS处理的动物中注射平衡盐溶液（BSS）相比，注射GLN导致肺组织中HSP - 70显著增加。在肺上皮细胞和巨噬细胞中观察到HSP - 70表达增加。GLN显著改善了LPS处理后肺组织中三磷酸腺苷与二磷酸腺苷的比值。槲皮素抑制了GLN介导的肺组织中HSP - 70的增加，并阻断了GLN对LPS处理后三磷酸腺苷与二磷酸腺苷比值的有益作用。
单剂量的GLN可增强亚致死性内毒素血症后肺上皮细胞和巨噬细胞中的HSP - 70。此外，GLN可减轻内毒素诱导的肺代谢功能障碍。GLN对亚致死性内毒素血症引起的代谢功能障碍后肺组织的有益作用可能部分由增强的HSP - 70介导。
