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脓毒症期间,细胞内谷氨酰胺是否调节肌肉蛋白质周转?

Is muscle protein turnover regulated by intracellular glutamine during sepsis?

作者信息

Fang C H, James J H, Fischer J E, Hasselgren P O

机构信息

Department of Surgery, University of Cincinnati, Ohio, USA.

出版信息

JPEN J Parenter Enteral Nutr. 1995 Jul-Aug;19(4):279-85. doi: 10.1177/0148607195019004279.

DOI:10.1177/0148607195019004279
PMID:8523626
Abstract

BACKGROUND

Low muscle glutamine levels during sepsis are associated with reduced protein synthesis and elevated protein breakdown, in particular myofibrillar protein breakdown. It is not known if this is a causal or coincidental relationship. We tested the hypothesis that muscle protein turnover rates are directly regulated by glutamine.

METHODS

Paired extensor digitorum longus muscles from nonseptic (sham-operated) and septic rats (16 hours after cecal ligation and puncture) were incubated in the absence or presence of 15 mmol glutamine/L. The effect of glutamine was tested in unsupplemented medium or in medium containing 1 mU/mL of insulin or a mixture of amino acids at normal plasma concentrations. Protein synthesis was measured as incorporation of 14C-phenylalanine into protein; total and myofibrillar protein breakdown was determined by measuring tyrosine and 3-methylhistidine, respectively.

RESULTS

Muscles accumulated intracellular glutamine well above normal concentrations in the presence of 15 mmol glutamine/L. In spite of this, protein synthesis was not affected by glutamine, neither when muscles were incubated in unsupplemented medium nor in medium containing insulin or amino acid mixture. Total protein breakdown was not influenced by glutamine when muscles were incubated in unsupplemented medium or with insulin but was reduced by glutamine in the presence of an amino acid mixture. Myofibrillar protein breakdown was unaffected by glutamine in unsupplemented medium and in medium containing insulin but was increased by glutamine in the presence of amino acid mixture.

CONCLUSION

Reduced muscle protein synthesis and increased myofibrillar protein breakdown during sepsis are probably not caused by the low intracellular glutamine levels noticed in this condition.

摘要

背景

脓毒症期间肌肉谷氨酰胺水平降低与蛋白质合成减少及蛋白质分解增加有关,尤其是肌原纤维蛋白分解。尚不清楚这是因果关系还是巧合。我们检验了肌肉蛋白质周转率直接受谷氨酰胺调节的假说。

方法

将来自非脓毒症(假手术)大鼠和脓毒症大鼠(盲肠结扎和穿刺术后16小时)的成对趾长伸肌在不存在或存在15 mmol/L谷氨酰胺的情况下孵育。在未补充培养基中或含有1 mU/mL胰岛素或正常血浆浓度氨基酸混合物的培养基中测试谷氨酰胺的作用。蛋白质合成通过测量14C-苯丙氨酸掺入蛋白质来测定;总蛋白和肌原纤维蛋白分解分别通过测量酪氨酸和3-甲基组氨酸来确定。

结果

在存在15 mmol/L谷氨酰胺的情况下,肌肉细胞内谷氨酰胺积累远高于正常浓度。尽管如此,无论肌肉在未补充培养基中孵育,还是在含有胰岛素或氨基酸混合物的培养基中孵育,蛋白质合成均不受谷氨酰胺影响。当肌肉在未补充培养基中或与胰岛素一起孵育时,总蛋白分解不受谷氨酰胺影响,但在存在氨基酸混合物时,谷氨酰胺可使其降低。在未补充培养基和含有胰岛素的培养基中,肌原纤维蛋白分解不受谷氨酰胺影响,但在存在氨基酸混合物时,谷氨酰胺可使其增加。

结论

脓毒症期间肌肉蛋白质合成减少和肌原纤维蛋白分解增加可能不是由这种情况下细胞内谷氨酰胺水平降低引起的。

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