Marchesini G, Bianchi G P, Vilstrup H, Checchia G A, Patrono D, Zoli M
J Hepatol. 1987 Feb;4(1):108-17. doi: 10.1016/s0168-8278(87)80017-x.
In an attempt to clarify the pathogenesis of the decreased branched-chain amino acid (BCAA) plasma concentrations in cirrhosis, the plasma clearances were measured in 7 patients with cirrhosis and in 7 age- and sex-matched control subjects. BCAA were given as prime-continuous infusions. The plasma clearances of valine, isoleucine, and leucine, calculated as infusion rate divided by steady state concentration, were low normal in cirrhotics despite hyperinsulinaemia, but different BCAA had different clearances (P less than 0.01). The endogenous basal appearance rates of BCAA, estimated by the basal concentrations multiplied by the plasma clearances, were lower in cirrhotics (P less than 0.025). The apparent theoretical volumes of distribution of BCAA, assessed by the ratio between the clearance and the concentration decay constant after infusion stop, were on average 67% of the total body weight, and were neither different among the three BCAA, nor between the two groups. The urea nitrogen synthesis rate did not increase significantly, suggesting that most of the infused BCAA nitrogen was taken up in peripheral tissues. The decreased concentration of BCAA in cirrhotics (394 +/- 81 mumol/l (mean +/- SD) in the present series vs 510 +/- 68 in controls; P less than 0.025) is not attributable to changes in plasma clearance. The most likely explanation is decreased afflux of BCAA into plasma.
为了阐明肝硬化患者血浆中支链氨基酸(BCAA)浓度降低的发病机制,我们对7例肝硬化患者和7例年龄及性别匹配的对照者进行了血浆清除率测定。BCAA采用单次连续输注给药。以输注速率除以稳态浓度计算得出的缬氨酸、异亮氨酸和亮氨酸的血浆清除率,在肝硬化患者中虽有高胰岛素血症但仍处于正常低限,不过不同支链氨基酸的清除率有所不同(P<0.01)。通过基础浓度乘以血浆清除率估算的BCAA内源性基础出现率,在肝硬化患者中较低(P<0.025)。BCAA的表观理论分布容积,通过输注停止后清除率与浓度衰减常数的比值评估,平均为总体重的67%,在三种支链氨基酸之间以及两组之间均无差异。尿素氮合成率未显著增加,这表明输注的大部分BCAA氮被外周组织摄取。肝硬化患者BCAA浓度降低(本系列中为394±81μmol/L(均值±标准差),而对照组为510±68;P<0.025)并非归因于血浆清除率的变化。最可能的解释是BCAA流入血浆减少。