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慢性阻塞性肺疾病中外侧股四头肌代谢及转运体特征的改变

Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease.

作者信息

Green H J, Burnett M E, D'Arsigny C L, O'Donnell D E, Ouyang J, Webb K A

机构信息

Dept. of Kinesiology, Univ. of Waterloo, Waterloo, Ontario, Canada N2L 3G1.

出版信息

J Appl Physiol (1985). 2008 Sep;105(3):879-86. doi: 10.1152/japplphysiol.90458.2008. Epub 2008 Jul 17.

Abstract

To investigate energy metabolic and transporter characteristics in resting muscle of patients with moderate to severe chronic obstructive pulmonary disease [COPD; forced expiratory volume in 1 s (FEV(1)) = 42 +/- 6.0% (mean +/- SE)], tissue was extracted from resting vastus lateralis (VL) of 9 COPD patients and compared with that of 12 healthy control subjects (FEV(1) = 114 +/- 3.4%). Compared with controls, lower (P < 0.05) concentrations (mmol/kg dry wt) of ATP (19.6 +/- 0.65 vs. 17.8 +/- 0.69) and phosphocreatine (81.3 +/- 2.3 vs. 69.1 +/- 4.2) were observed in COPD, which occurred in the absence of differences in the total adenine nucleotide and total creatine pools. Higher concentrations were observed in COPD for several glycolytic metabolites (glucose-1-phosphate, glucose-6-phosphate, fructose-6-phosphate, pyruvate) but not lactate. Glycogen storage was not affected by the disease (289 +/- 20 vs. 269 +/- 20 mmol glucosyl units/kg dry wt). Although no difference between groups was observed for the glucose transporter GLUT1, GLUT4 was reduced by 28% in COPD. For the monocarboxylate transporters, MCT4 was 35% lower in COPD, with no differences observed for MCT1. These results indicate that in resting VL, moderate to severe COPD results in a reduction in phosphorylation potential, an apparent elevation of glycolytic flux rate, and a potential defect in glucose and lactate transport as a result of reduced levels of the principal isoforms.

摘要

为研究中重度慢性阻塞性肺疾病(COPD;1秒用力呼气容积[FEV(1)] = 42±6.0%[平均值±标准误])患者静息肌肉的能量代谢及转运体特征,从9例COPD患者的静息股外侧肌(VL)中提取组织,并与12例健康对照者(FEV(1) = 114±3.4%)的组织进行比较。与对照组相比,COPD患者的ATP(19.6±0.65对17.8±0.69)和磷酸肌酸(81.3±2.3对69.1±4.2)浓度(mmol/kg干重)较低(P < 0.05),而总腺嘌呤核苷酸池和总肌酸池无差异。COPD患者的几种糖酵解代谢物(葡萄糖-1-磷酸、葡萄糖-6-磷酸、果糖-6-磷酸、丙酮酸)浓度较高,但乳酸浓度未升高。糖原储存不受该疾病影响(289±20对269±20 mmol葡萄糖基单位/kg干重)。尽管两组之间葡萄糖转运体GLUT1无差异,但COPD患者的GLUT4减少了28%。对于单羧酸转运体,COPD患者的MCT4降低了35%,而MCT1无差异。这些结果表明,在静息VL中,中重度COPD导致磷酸化电位降低、糖酵解通量率明显升高,以及由于主要异构体水平降低导致葡萄糖和乳酸转运存在潜在缺陷。

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