Binding of bilirubin and bromosulphthalein to albumin: Implications for understanding the pathophysiology of liver failure and its management
Binding of bilirubin and bromosulphthalein to albumin: Implications for understanding the pathophysiology of liver failure and its management
复制标题
DOI：
10.1002/lt.20323
复制
发表时间：
2004-12-01
影响因子：
4.6
通讯作者：
Jalan, R
中科院分区：
文献类型：
--
作者：
Steiner, C;Sen, S;Jalan, R
白蛋白的结合/转运功能为在肝衰竭中使用白蛋白透析（例如分子吸附剂再循环系统 [MARS]）提供了理论基础。这项研究在体外研究了这些特性，并在体内验证了这些发现。将体外溴磺胺 (BSP) 和胆红素加标血浆针对白蛋白进行透析并取样。对以下患者进行了体内血清生化分析： 7 名接受 MARS 治疗的肝衰竭患者；来自 MARS 登记处的 98 名接受 MARS 治疗的患者； 8名患者接受白蛋白输注。体外 BSP 浓度未达到平衡，但 BSP 与白蛋白的摩尔比 (C-BSP/C-alb) 达到平衡，并且没有随后的跨膜转运，表明 C-BSP/C-alb 梯度（而不是简单扩散）驱动 BSP 转运。胆红素的运输方式类似。 MARS 期间体内血清胆红素降低 (n = 26) 与治疗前胆红素相关 (r = 0.42)，但与治疗前胆红素与白蛋白摩尔比 (C-胆红素/C-alb) 相关性更好 (r = 0.85)。最强的相关性是 C-胆红素/C-白蛋白、降低和治疗前 C-胆红素/C-白蛋白之间的相关性 (r = 0.9)。在 MARS 登记患者中也观察到了类似的模式。白蛋白输注后（n = 8），血清白蛋白和胆红素均升高，而 C-胆红素 C-alb 保持不变。 C-胆红素似乎在白蛋白透析中很重要，并且通常在肝病患者中很重要，这增强了白蛋白的毒素结合功能在肝病中的重要性。
The binding/transporting functions of albumin provide the rationale for using albumin dialysis (e.g., molecular adsorbents recirculating system [MARS]) in liver failure. This study investigates these properties in vitro, validating the findings in vivo. In vitro bromosulphthalein (BSP) and bilirubin-spiked plasma were dialyzed against albumin and sampled. In vivo serum biochemistry was analyzed in: 7 MARS-treated liver failure patients; 98 MARS-treated patients from the MARS Registry; and 8 patients receiving albumin infusion. In vitro BSP concentrations did not equilibrate, but the molar ratio of BSP to albumin (C-BSP/C-alb) did, with no subsequent transmembrane transport, suggesting that the C-BSP/C-alb, gradient (rather than simple diffusion) drives BSP transport. Bilirubin was transported similarly. In vivo serum bilirubin reduction during MARS sessions (n = 26) correlated with pre-treatment bilirubin (r = 0.42), but better (r = 0.85) with pre-treatment molar ratio of bilirubin to albumin (C-bilirubin/C-alb). The strongest correlation was between C-bilirubin/C-alb, reduction and pre-treatment C-bilirubin/C-alb (r = 0.9). A similar pattern was observed in the MARS Registry patients. After albumin infusion (n = 8), both serum albumin and bilirubin increased, while C-bilirubin C-alb remained unchanged. C-bilirubin appears to be important in albumin dialysis, and generally in liver disease patients, reinforcing the importance of the toxinbinding functions of albumin in liver disease.