Walsh T R, Rao P N, Makowka L, Starzl T E
Department of Surgery, University of Pittsburgh, Pennsylvania 15261.
J Surg Res. 1990 Jul;49(1):18-22. doi: 10.1016/0022-4804(90)90104-a.
A proposed mechanism for irreversible ischemic liver damage has been peroxidation of membrane phospholipids by free radicals. However, the hepatocyte is laden with enzymes which are antioxidants and, therefore, ought to be relatively resistant to oxidative injury. To test the hypothesis that free radical damage from ischemia and reperfusion of the liver is a nonparenchymal cell process, we studied an in vivo model of ischemia. A point of transition from reversible to irreversible ischemia was defined at greater than or equal to 60 min of total ischemia by serial measurements of ATP at control, end of ischemia, and end of reperfusion periods (n = 6 each). Nonparenchymal cells were separated out of 10 livers in each ischemic group using a Percoll gradient. Second derivative spectroscopy did not detect conjugated dienes in any hepatocellular fraction, total cellular, mitochondrial, or microsomal, but did in the nonparenchymal cell fractions of livers from the 60- and 90-min ischemia groups. This in vivo study shows that irreversible ischemia in the rat liver is associated with free radical lipid peroxidation, but that the nonparenchymal cells rather than hepatocytes are the focus of this injury.
一种关于不可逆性缺血性肝损伤的推测机制是自由基导致膜磷脂过氧化。然而，肝细胞富含抗氧化酶，因此应该相对抵抗氧化损伤。为了验证肝脏缺血再灌注产生的自由基损伤是一种非实质细胞过程的假说，我们研究了一种缺血的体内模型。通过在对照期、缺血末期和再灌注末期连续测量ATP（每组n = 6），将总缺血时间大于或等于60分钟定义为从可逆性缺血向不可逆性缺血转变的时间点。使用Percoll梯度从每个缺血组的10个肝脏中分离出非实质细胞。二阶导数光谱法在任何肝细胞组分（总细胞、线粒体或微粒体）中均未检测到共轭二烯，但在60分钟和90分钟缺血组肝脏的非实质细胞组分中检测到了共轭二烯。这项体内研究表明，大鼠肝脏的不可逆性缺血与自由基脂质过氧化有关，但这种损伤的焦点是非实质细胞而非肝细胞。
