French S W, Benson N C, Sun P S
Hepatology. 1984 Sep-Oct;4(5):912-7. doi: 10.1002/hep.1840040521.
Rats fed ethanol from 21 to 130 days were subjected to one or more episodes of hypoxia (6% O2) in order to determine if ethanol predisposed to centrilobular liver necrosis induced by hypoxia. Pair-fed control rats were fed the diet regimen in parallel with the ethanol-fed rats through an indwelling gastric cannula. The diet and ethanol were fed continuously 24 hr per day so as to maintain high blood alcohol levels in the ethanol-fed rats. Serum enzyme levels, SGOT and SGPT were measured before and after the hypoxic episodes as an indicator of centrilobular necrosis. Animal livers were studied for centrilobular necrosis by light and electron microscopy. Necrosis was documented to be present when flocculent densities were found in hepatocytic mitochondria or the plasma membrane permitted lanthanum entrance into the cell. The results showed that ethanol feeding to maintain high blood alcohol levels did increase the propensity of the liver to undergo centrilobular necrosis when the rats were subjected to hypoxia (1 hr 45 min to 5 hr 30 min). Centrilobular necrosis was observed in the ethanol-fed rats only. Serum enzyme levels (SGPT and SGOT) rose to very high levels in these rats when they were permitted to die of hypoxia. Serum sediment from the ethanol-fed rats contained numerous cell fragments and free organelles. Since the plasma membranes were missing along the sinusoidal face of centrilobular hepatocytes and microbodies were present, it was concluded that the cell fragments in the blood had originated from necrotic hepatocytes.
给21至130日龄的大鼠喂食乙醇，使其经历一次或多次缺氧发作（6%氧气），以确定乙醇是否易引发由缺氧诱导的小叶中心性肝坏死。配对喂食的对照大鼠通过留置胃管与喂食乙醇的大鼠并行喂食相同的饮食方案。每天24小时持续喂食饮食和乙醇，以维持喂食乙醇大鼠的高血醇水平。在缺氧发作前后测量血清酶水平，即谷草转氨酶（SGOT）和谷丙转氨酶（SGPT），作为小叶中心坏死的指标。通过光学显微镜和电子显微镜对动物肝脏进行小叶中心坏死研究。当在肝细胞线粒体中发现絮状密度或质膜允许镧进入细胞时，记录为存在坏死。结果表明，当大鼠处于缺氧状态（1小时45分钟至5小时30分钟）时，喂食乙醇以维持高血醇水平确实增加了肝脏发生小叶中心坏死的倾向。仅在喂食乙醇的大鼠中观察到小叶中心坏死。当这些大鼠因缺氧死亡时，其血清酶水平（SGPT和SGOT）升至非常高的水平。喂食乙醇的大鼠的血清沉淀物含有大量细胞碎片和游离细胞器。由于小叶中心肝细胞窦状面的质膜缺失且存在微体，得出结论：血液中的细胞碎片源自坏死的肝细胞。
