Clinical and experimental studies on protein metabolism in acute hepatic failure-with special relation to effects of branched-chain amino acid infusion

1)临床研究对12例重型肝炎（FH）、12例重型急性肝炎（AHS）和8例健康对照者（HC）分别于静息时和输注支链氨基酸（BCAA）溶液（总氨基酸83.6g/L，Fischer’s比37.1500ml，2 hr）后1h进行间接量热法测定。测量能量消耗（千卡/天和标准化为估计基础代谢率的比率; EE/BMR）和碳水化合物、脂肪和蛋白质的氧化体积（g/天）。FH和AHS患者的EE/BMR显著高于HC患者。BCAA输注可显著提高中度代谢FH、AHS和HC患者的EE/BMR，但对高代谢FH的指标无影响。BCAA输注可增加中度代谢FH、AHS和HC患者的蛋白质氧化量，但对高代谢FH无影响。支链氨基酸可作为能量底物用于AHS患者和FH患者， ...更多信息 y代谢状态。在AHF患者中使用BCAA输注，预先精确分析能量代谢是必不可少的。2）实验研究通过静脉内给予脂多糖和腹腔内给予D-氨基半乳糖盐酸盐在雄性东柳大鼠中诱导AHF。从注射后18小时开始，AHF和对照大鼠静脉注射以下5种溶液之一，持续6小时：1）盐水，2）10%葡萄糖，3）标准10%氨基酸配方，总氮含量为12.2g/L，支链氨基酸/芳香族氨基酸摩尔比为37.05，4）氮含量为21.9g/L且比率为148.2的富含BCAA的溶液，或5）活性安慰剂相对于氮含量为21.9g/L且比率为37.05的富含BCAA的溶液。同时，每组给予持续输注14 <14>C-亮氨酸，根据动力学模型分析蛋白质周转。与对照组相比，AHF的总蛋白周转率（总流量）、氧化和分解率均显著增加，与生理盐水或10%葡萄糖的作用相比，标准10%氨基酸配方、富含BCAA的溶液或安慰剂在AHF中显著增加总流量和氧化。虽然生理盐水、10%葡萄糖、标准10%氨基酸配方和安慰剂对合成速率没有影响，但富含支链氨基酸的溶液显著增加了合成速率。任何溶液均未抑制击穿。这些结果表明，大鼠与AHF是在catebolic状态和任何三种氨基酸的解决方案可以被氧化，以提供能量在AHF。此外，BCAA富集的溶液的输液可能有一个特定的蛋白质节约效果，通过增加蛋白质的合成。少

1) Clinical studyIndirect calorimetry was performed at resting and at 1 hour after infusion of branched-chain amino acid (BCAA) solution (83.6g total amino acids/L,Fischer's ratio 37.1,500ml for 2hr) in 12 patients with fulminant hepatitis (FH), 12 patients with severe type of acute hepatitis (AHS), and 8 healthy controls (HC). Energy expenditure (Kcal/day and a ratio standardized to the estimated basal metabolic rate ; EE/BMR) and oxidation volumes of carbohydrate, fat and protein (g/day) were measured. EE/BMR was significantly higher in patients with FH and in those with AHS than in HC.Infusion of BCAA significantly raised EE/BMR in moderately metabolic FH,in AHS and in HC,although it did not affect the index in hypermetabolic FH.Increases in the protein oxidation volume were brought by BCAA infusion in moderately metabolic FH,in AHS and in HC but not in hypermetabolic FH.In conclusion, BCAA can be utilized as an energy substrate in patients with AHS and in cases of FH with moderatel … More y metabolic state. Precise analysis of energy metabolism is essential in advance, with a use of BCAA infusion in patients with AHF.2) Experimental studyAHF was induced in male Donryu rats by giving lypopolysaccaride intravenously and D-galactosamine hydrochloride intraperitoneally. From 18 hours after injection, AHF and control rats were given one of the following five solutions intravenously for 6 hours : 1) saline, 2) 10% glucose, 3) standard 10% amino acid formula with total nitrogen content of 12.2g/L and BCAA/aromatic amino acid molar ratio of 37.05,4) BCAA-enriched solution with nitrogen content of 21.9g/L and the ratio of 148.2, or 5) an active placebo against BCAA-enriched solution with nitrogen content of 21.9g/L and the ratio of 37.05. In parallel, each group was given a continuous infusion of ^<14>C-leucine, protein turnover was analyzed according to the kinetic model. When compared with the control, rates of total protein turnover (total flux), oxidation and breakdown all increased significantly in AHF.Infusion of standard 10% amino acid formula, BCAA-enriched solution or the placebo in AHF increased total flux and oxidation significantly as compared with the effect of saline or 10% glucose. Although saline, 10% glucose, standard 10% amino acid formula, and the placebo had no effect on synthesis rate, it was increased significantly with BCAA-enriched solution. Breakdown was not suppressed with any solutions. These results suggest that rats with AHF are in a catebolic state and that any of the three amino acid solutions can be oxidized to provide energy in AHF.In addition, infusion of BCAA-enriched solution may have a specific protein-sparing effect by increasing the protein synthesis. Less