Prod'homme Magali, Rochon Cécile, Balage Michèle, Laurichesse Henri, Tauveron Igor, Champredon Claude, Thieblot Philippe, Beytout Jean, Grizard Jean
Unité de Nutrition et Métabolisme Protéique, Institut National de la Recherche Agronomique, Clermont-Ferrand/Theix, Saint-Genès-Champanelle, France.
Am J Physiol Endocrinol Metab. 2006 Apr;290(4):E685-93. doi: 10.1152/ajpendo.00067.2005. Epub 2005 Oct 25.
The present study was carried out to assess the effects of protease inhibitor (PI) therapy on basal whole body protein metabolism and its response to acute amino acid-glucose infusion in 14 human immunodeficiency virus (HIV)-infected patients. Patients treated with PIs (PI+, 7 patients) or without PIs (PI-, 7 patients) were studied after an overnight fast during a 180-min basal period followed by a 140-min period of amino acid-glucose infusion. Protein metabolism was investigated by a primed constant infusion of l-[1-(13)C]leucine. Dual-energy X-ray absorptiometry for determination of fat-free mass (FFM) and body fat mass measured body composition. In the postabsorptive state, whole body leucine balance was 2.5 times (P < 0.05) less negative in the PI+ than in the PI- group. In HIV-infected patients treated with PIs, the oxidative leucine disposal during an acute amino acid-glucose infusion was lower (0.58 +/- 0.09 vs. 0.81 +/- 0.07 micromol x kg FFM(-1) x min(-1) using plasma [(13)C]leucine enrichment, P = 0.06; or 0.70 +/- 0.10 vs. 0.99 +/- 0.08 micromol x kg FFM(-1) x min(-1) using plasma [(13)C]ketoisocaproic acid enrichment, P = 0.04 in PI+ and PI- groups, respectively) than in patients treated without PIs. Consequently, whole body nonoxidative leucine disposal (an index of protein synthesis) and leucine balance (0.50 +/- 0.10 vs. 0.18 +/- 0.06 micromol x kg FFM x (-1) x min(-1) in PI+ and PI- groups respectively, P < 0.05) were significantly improved during amino acid-glucose infusion in patients treated with PIs. However, whereas the response of whole body protein anabolism to an amino acid-glucose infusion was increased in HIV-infected patients treated with PIs, any improvement in lean body mass was detected.
本研究旨在评估蛋白酶抑制剂（PI）疗法对14例人类免疫缺陷病毒（HIV）感染患者基础全身蛋白质代谢及其对急性氨基酸 - 葡萄糖输注反应的影响。在180分钟的基础期过夜禁食后，接着进行140分钟的氨基酸 - 葡萄糖输注，对接受PI治疗的患者（PI +，7例）和未接受PI治疗的患者（PI -，7例）进行研究。通过一次性静脉注射l - [1 - （13）C]亮氨酸来研究蛋白质代谢。采用双能X线吸收法测定去脂体重（FFM）和体脂肪量以评估身体组成。在吸收后状态下，PI +组的全身亮氨酸平衡的负性程度比PI -组低2.5倍（P < 0.05）。在接受PI治疗的HIV感染患者中，急性氨基酸 - 葡萄糖输注期间亮氨酸的氧化代谢率较低（使用血浆[（13）C]亮氨酸丰度时，PI +组为0.58±0.09 vs. PI -组为0.81±0.07 μmol·kg FFM（-1）·min（-1），P = 0.06；使用血浆[（13）C]酮异己酸丰度时，PI +组为0.70±0.10 vs. PI -组为0.99±0.08 μmol·kg FFM（-1）·min（-1），PI +组和PI -组P值分别为0.04），低于未接受PI治疗的患者。因此，在氨基酸 - 葡萄糖输注期间，接受PI治疗的患者全身非氧化亮氨酸代谢率（蛋白质合成指标）和亮氨酸平衡（PI +组和PI -组分别为0.50±0.10 vs. 0.18±0.06 μmol·kg FFM（-1）·min（-1），P < 0.05）显著改善。然而，虽然接受PI治疗的HIV感染患者全身蛋白质合成代谢对氨基酸 - 葡萄糖输注的反应有所增加，但未检测到瘦体重有任何改善。
