Sutherland D E, Numata M, Matas A J, Simmons R L, Najarian J S
Surgery. 1977 Jul;82(1):124-32.
Acute liver failure carries a high rate of mortality, but if metabolic support can be maintained for a critical period, liver healing and recovery are possible. Current techniques of temporary hepatic support are cumbersome and inconsistently effective. We studied the ability of dispersed hepatocytes to provide metabolic support when transplanted to rats with liver failure induced by dimethylnitrosamine (DMNA), a rapidly metabolized agent that is selectively toxic to liver cells. DMNA (20 mg/kg) was administered intravenously to 92 Lewis rats. Animals were divided into four groups receiving the following treatments 24 hours after DMNA administration: group I-intraperitoneal transplantation of hepatocytes prepared from 2.0 gm of normal isologous rat liver; group II-infusion into the portal vein of hepatocytes prepared from 1.5 gm of liver; group III-infusion of saline into the portal vein; group IV-no further treatment. The percentages surviving in each group 3 weeks after DMNA administration were 63%, 71%, 17%, and 6%, respectively. Mean serum glutamic oxaloacetic transaminase (SGOT) levels 3 days after DMNA administration were similar in the four groups, indicating that the degree of liver damage was equivalent. A significantly higher proportion of hepatocyte treated rats survived. Liver histology after DMNA administration showed hemorrhagic central lobular necrosis. A return to near-normal architecture occurred by 3 weeks in surviving animals. In group II hepatocytes were seen in portal venules, sinusoids, and central veins. We conclude that dispersed hepatocytes, transplanted either intraperitoneally or via the portal vein, can provide sufficient metabolic support to allow for recovery from drug-induced hepatic necrosis.
急性肝衰竭死亡率很高，但如果能在关键时期维持代谢支持，肝脏就有可能愈合和恢复。目前的临时肝脏支持技术繁琐且效果不一。我们研究了将分散的肝细胞移植到由二甲基亚硝胺（DMNA）诱导肝衰竭的大鼠体内时，其提供代谢支持的能力。DMNA是一种快速代谢的物质，对肝细胞具有选择性毒性。将DMNA（20mg/kg）静脉注射给92只Lewis大鼠。动物在注射DMNA 24小时后被分为四组，接受以下治疗：第一组——腹腔内移植从2.0克正常同种大鼠肝脏制备的肝细胞；第二组——将从1.5克肝脏制备的肝细胞注入门静脉；第三组——向门静脉注入生理盐水；第四组——不进行进一步治疗。注射DMNA 3周后，每组的存活百分比分别为63%、71%、17%和6%。注射DMNA 3天后，四组的平均血清谷氨酸草酰乙酸转氨酶（SGOT）水平相似，表明肝损伤程度相当。接受肝细胞治疗的大鼠存活比例显著更高。注射DMNA后的肝脏组织学显示出血性中央小叶坏死。存活动物在3周时恢复到接近正常的结构。在第二组中，在门静脉小静脉、肝血窦和中央静脉中可见肝细胞。我们得出结论，腹腔内或通过门静脉移植的分散肝细胞可以提供足够的代谢支持，使药物诱导的肝坏死得以恢复。
