Elsing C, Reichen J, Marti U, Renner E L
Department of Clinical Pharmacology, University of Berne, Switzerland.
Gastroenterology. 1994 Aug;107(2):468-78. doi: 10.1016/0016-5085(94)90173-2.
BACKGROUND/AIMS: Rat hepatocyte Na+/H+ exchange is activated in vitro by growth factors and in vivo following partial hepatectomy. This study explored by which mechanism(s) it is activated in a cirrhosis model characterized by chronic stimulation of hepatocyte proliferation.
Rat hepatocytes were isolated 4 weeks after bile duct ligation or sham operation. Intracellular pH (pHi) was fluorimetrically determined, and plasma membranes and messenger RNA (mRNA) were prepared from isolated hepatocytes by standard methods.
Resting pHi was higher in bile duct-ligated than in control rats (7.42 +/- 0.03 vs. 7.06 +/- 0.04; P < 0.001). Although plasma membrane lipid composition and intracellular buffering capacity were similar, initial Na+/H+ exchange-mediated rates of pHi recovery following acid loading were higher in bile duct-ligated than in control rats (0.098 +/- 0.011 vs. 0.055 +/- 0.005 pH units/min; P < 0.05). The antiporter's set point was shifted approximately 0.3 pH units towards more alkaline values and its steady-state mRNA levels were doubled after bile duct ligation.
Hepatocellular Na+/H+ exchange is transcriptionally and posttranscriptionally activated in rat biliary cirrhosis further supporting a relationship between hepatocyte proliferation and Na+/H+ exchange activation.
背景/目的：大鼠肝细胞钠氢交换在体外可被生长因子激活，在体内部分肝切除术后也可被激活。本研究探讨在以肝细胞增殖长期受刺激为特征的肝硬化模型中，该交换是通过何种机制被激活的。
在胆管结扎或假手术后4周分离大鼠肝细胞。通过荧光法测定细胞内pH（pHi），并采用标准方法从分离的肝细胞中制备质膜和信使核糖核酸（mRNA）。
胆管结扎大鼠的静息pHi高于对照大鼠（7.42±0.03对7.06±0.04；P<0.001）。尽管质膜脂质组成和细胞内缓冲能力相似，但胆管结扎大鼠在酸负荷后最初由钠氢交换介导的pHi恢复速率高于对照大鼠（0.098±0.011对0.055±0.005pH单位/分钟；P<0.05）。反向转运体的设定点向更碱性的值移动了约0.3个pH单位，且其稳态mRNA水平在胆管结扎后增加了一倍。
大鼠胆汁性肝硬化中肝细胞钠氢交换在转录和转录后水平均被激活，进一步支持了肝细胞增殖与钠氢交换激活之间的关系。
