Dällenbach A, Marti U, Renner E L
Department of Clinical Pharmacology, University of Berne, Switzerland.
Hepatology. 1994 May;19(5):1290-301. doi: 10.1002/hep.1840190530.
In hepatocytes in vitro, Na+/H+ exchange, an important regulator of intracellular pH, is activated by epidermal growth factor, but its activity during liver regeneration in vivo is unknown. We therefore compared activity and regulation of Na+/H+ exchange in hepatocytes isolated after two-thirds partial hepatectomy or sham surgery, respectively, by measuring intracellular pH (fluorimetry) and steady state Na+/H+ exchange mRNA levels (Northern blotting). Resting intracellular pH increased from 7.06 +/- 0.02 to 7.12 +/- 0.02 (p < 0.05) 2 hr but not 20 hr after partial hepatectomy. Na+/H+ exchange-mediated rates of intracellular pH recovery from an acid load increased from 0.075 +/- 0.018 to 0.151 +/- 0.018 pH units/min (p < 0.05) 2 hr but not 20 hr after partial hepatectomy. Because intracellular buffering capacity was not affected, this reflects increased Na+/H+ exchange activity. The inverse relationship between Na+/H+ exchange activity and intracellular pH was shifted by about 0.1 pH units toward more alkaline pH values 2 hr but not 20 hr after partial hepatectomy, whereas steady-state Na+/H+ exchange mRNA levels remained unchanged. In conclusion, hepatocellular Na+/H+ exchange is activated early, transiently and at a posttranscriptional level during liver regeneration induced in the rat by partial hepatectomy.
在体外培养的肝细胞中,钠氢交换体(Na⁺/H⁺ exchange)是细胞内pH值的重要调节因子,可被表皮生长因子激活,但其在体内肝再生过程中的活性尚不清楚。因此,我们分别通过测量细胞内pH值(荧光测定法)和稳态钠氢交换体mRNA水平(Northern印迹法),比较了三分之二肝部分切除术后或假手术后分离的肝细胞中钠氢交换体的活性及其调节情况。肝部分切除术后2小时而非20小时,静息细胞内pH值从7.06±0.02升至7.12±0.02(p<0.05)。肝部分切除术后2小时而非20小时,钠氢交换体介导的细胞内pH值从酸负荷中恢复的速率从0.075±0.018增至0.151±0.018pH单位/分钟(p<0.05)。由于细胞内缓冲能力未受影响,这反映了钠氢交换体活性增强。肝部分切除术后2小时而非20小时,钠氢交换体活性与细胞内pH值之间的反比关系向更碱性的pH值方向移动了约0.1pH单位,而稳态钠氢交换体mRNA水平保持不变。总之,在大鼠肝部分切除诱导的肝再生过程中,肝细胞钠氢交换体在转录后水平被早期、短暂激活。