Yang Gang, Zhang Yong, Wu Dan, Wang Chao, Yang Yong-Jun, Fan Shi-Jun, Xia Lin, Wei Yan, Peng Xi
Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University) Chongqing 400038, PR China.
Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University) Chongqing 400038, PR China.
Am J Transl Res. 2019 Dec 15;11(12):7286-7299. eCollection 2019.
Glutamine is an important amino acid that plays a crucial role in nutritional therapy for patients with burns, but its effects on post-burn metabolism and the underlying mechanisms are unclear. In this study, H nuclear magnetic resonance spectroscopy (H-NMR) was used to examine the effects of glutamine on plasma metabolites in burned rats and to explore the underlying mechanisms. After burn injury, the rats exhibited significant increases in resting energy expenditure (REE) and hypercatabolism, and anabolism was inhibited. The levels of metabolites that reflect the proteolysis of skeletal muscle, such as alanine, histidine, leucine, valine, 3-methylhistidine and creatine, were significantly increased. In addition, the burned rats exhibited energy synthesis dysfunction, as evidenced by a decrease in the ATP concentration and increased levels of lactic acid. Notably, the concentration of α-ketoisovalerate, which reflects the function of the mitochondrial membrane, was significantly increased, suggesting an impairment in mitochondrial function and inhibition of oxidative phosphorylation. Glutamine administration significantly alleviated post-burn hypermetabolism and inhibited proteolysis in skeletal muscle. Consequently, the levels of glutamine metabolites, such as glutamic acid and α-ketoglutarate, along with ATP synthesis were significantly increased, whereas alanine, leucine, 3-methylhistidine and lactic acid were significantly depleted. Furthermore, after glutamine administration, the synthesis of reductive compounds was increased, leading to significantly increased levels of reduced glutathione and NADPH. This process may be an important mechanism by which glutamine alleviates oxidative stress, promotes ATP synthesis, and reduces hypermetabolism after burn.
谷氨酰胺是一种重要的氨基酸,在烧伤患者的营养治疗中起着关键作用,但其对烧伤后代谢的影响及潜在机制尚不清楚。在本研究中,采用氢核磁共振波谱(H-NMR)检测谷氨酰胺对烧伤大鼠血浆代谢物的影响,并探讨其潜在机制。烧伤后,大鼠静息能量消耗(REE)显著增加,出现高分解代谢,合成代谢受到抑制。反映骨骼肌蛋白水解的代谢物水平,如丙氨酸、组氨酸、亮氨酸、缬氨酸、3-甲基组氨酸和肌酸,显著升高。此外,烧伤大鼠表现出能量合成功能障碍,ATP浓度降低和乳酸水平升高证明了这一点。值得注意的是,反映线粒体膜功能的α-酮异戊酸浓度显著升高,提示线粒体功能受损和氧化磷酸化受到抑制。给予谷氨酰胺可显著减轻烧伤后的高代谢状态,并抑制骨骼肌的蛋白水解。因此,谷氨酰胺代谢物如谷氨酸和α-酮戊二酸的水平以及ATP合成显著增加,而丙氨酸、亮氨酸、3-甲基组氨酸和乳酸则显著减少。此外,给予谷氨酰胺后,还原性化合物的合成增加,导致还原型谷胱甘肽和NADPH水平显著升高。这一过程可能是谷氨酰胺减轻烧伤后氧化应激、促进ATP合成和降低高代谢状态的重要机制。