Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Biochim Biophys Acta Mol Basis Dis. 2024 Aug;1870(6):167275. doi: 10.1016/j.bbadis.2024.167275. Epub 2024 Jun 4.
Albumin infusions improve circulatory and renal function in patients with decompensated cirrhosis. However, there is no convincing evidence that hypoalbuminemia contributes to ascites formation in liver cirrhosis. The aim of our study is to determine the exact role of hypoalbuminemia in the formation of ascites caused by liver cirrhosis and its underlying mechanism. Clinical profiles of patients with liver cirrhosis retrospectively analyzed. The details of albumin involved in ascites formation were investigated in rat model and murine model. Statistical analysis demonstrated hypoalbuminemia was an independent risk factor for ascites formation in patients with liver cirrhosis (OR = 0.722, P < 0.001). In carbon tetrachloride (CCl)-induced rat model of liver cirrhosis, a significant reduction in serum albumin was observed in rats with ascites (13.37 g/L) compared with rats without ascites (21.43 g/L, P < 0.001). In thioacetamide (TAA)-treated mice, ascites amount of heterozygous albumin (Alb) mice (112.0 mg) was larger than that of wild-type (Alb) mice (58.46 mg, P < 0.001). In CCl-induced chronic liver injury, ascites amounts of Alb or Alb mice were 80.00 mg or 48.46 mg (P = 0.001). Further study demonstrated 24-h urinary sodium excretion in Alb mice was lower than that of Alb mice in TAA/CCl-induce murine models of liver cirrhosis. Additionally, serum sodium concentration of Alb mice was lower than that of Alb mice. In cirrhotic mice, higher level of antidiuretic hormone was observed in Alb mice compared with the control; and renal aquaporin (AQP2) expression in Alb mice was significantly higher than that of WT mice. These revealed hypoalbuminemia contributed to the occurrence of ascites in liver cirrhosis through sodium and water retention.
白蛋白输注可改善失代偿期肝硬化患者的循环和肾功能。然而，没有令人信服的证据表明低白蛋白血症是肝硬化腹水形成的原因。本研究旨在确定低白蛋白血症在肝硬化腹水形成中的确切作用及其潜在机制。回顾性分析肝硬化患者的临床资料。在大鼠模型和小鼠模型中研究白蛋白在腹水形成中的作用机制。统计分析表明，低白蛋白血症是肝硬化患者腹水形成的独立危险因素（OR=0.722，P<0.001）。在四氯化碳（CCl）诱导的肝硬化大鼠模型中，有腹水的大鼠血清白蛋白显著降低（13.37 g/L），而无腹水的大鼠血清白蛋白水平较高（21.43 g/L，P<0.001）。在乙硫氨酸（TAA）处理的小鼠中，杂合白蛋白（Alb）小鼠的腹水量（112.0 mg）大于野生型（Alb）小鼠（58.46 mg，P<0.001）。在 CCl 诱导的慢性肝损伤中，Alb 或 Alb 小鼠的腹水量分别为 80.00 mg 或 48.46 mg（P=0.001）。进一步研究表明，在 TAA/CCl 诱导的肝纤维化小鼠模型中，Alb 小鼠的 24 小时尿钠排泄量低于 Alb 小鼠。此外，Alb 小鼠的血清钠浓度低于 Alb 小鼠。在肝硬化小鼠中，Alb 小鼠的抗利尿激素水平高于对照组；且 Alb 小鼠的肾水通道蛋白（AQP2）表达显著高于 WT 小鼠。这些结果表明，低白蛋白血症通过钠水潴留导致肝硬化腹水的发生。
