Villalobos-Molina R, Saavedra-Molina A, Devlin T M
Department of Biochemistry, Allegheny University of the Health Sciences, Philadelphia, PA, USA.
Arch Med Res. 1998 Autumn;29(3):219-23.
The mechanisms whereby rat hepatocytes undergo irreversible injury due to a lack of oxygen have not been established.
Liver cells were used for reperfusion injury, and four compartmentalized pathways were evaluated during hypoxia (N2/CO2, 19:1) for 30 min followed by oxygen (O2/CO2, 19:1) for 30 min.
Cell viability decreased during the hypoxic, but not during the reoxygenation, phase. Glycogenolysis, as measured by glucose release, was significantly increased during hypoxia as compared to controls in oxygen (205 +/- 15 vs. 155 +/- 10 nmol glucose/mg protein/h, respectively), and did not return to normal levels by reoxygenation. Gluconeogenesis was importantly decreased during hypoxia (102 +/- 10 vs. 8 +/- 2 nmol glucose/mg protein/h) with partial recovery during reoxygenation. Ureagenesis diminished in hypoxia, but recovered during reoxygenation. Additionally, 3-hydroxybutyrate formation was augmented by hypoxia, with some recovery when oxygen was present.
These results suggest that compartmentalized pathways are protected from hypoxic injury in isolated hepatocytes, and also suggest it as a model to test the idea that enzymes of those pathways are organized into multienzyme complexes in vivo.
大鼠肝细胞因缺氧而发生不可逆损伤的机制尚未明确。
将肝细胞用于再灌注损伤研究，在缺氧（氮气/二氧化碳，19:1）30分钟后再进行氧合（氧气/二氧化碳，19:1）30分钟，评估四个区室化途径。
在缺氧阶段细胞活力下降，但在复氧阶段未下降。与在氧气环境中的对照组相比，缺氧期间通过葡萄糖释放测定的糖原分解显著增加（分别为205±15与155±10纳摩尔葡萄糖/毫克蛋白/小时），且复氧后未恢复至正常水平。缺氧期间糖异生显著减少（102±10与8±2纳摩尔葡萄糖/毫克蛋白/小时），复氧时有部分恢复。尿素生成在缺氧时减少，但在复氧时恢复。此外，缺氧会增加3-羟基丁酸的形成，有氧气存在时会有一定程度的恢复。
这些结果表明，区室化途径在分离的肝细胞中免受缺氧损伤，也表明它可作为一个模型来检验这些途径的酶在体内被组织成多酶复合物这一观点。
