Kokudo N, Kothary P C, Eckhauser F E, Raper S E
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109.
J Surg Res. 1992 Jun;52(6):648-55. doi: 10.1016/0022-4804(92)90144-o.
Impaired liver regeneration in cirrhosis complicates the surgical treatment of liver tumors which arise in this setting. We developed a rat model to investigate the regenerative response of cirrhotic liver after hepatectomy and studied the effect of exogenous transforming growth factor-alpha (TGF-alpha), a potent liver mitogen. Micronodular cirrhosis was established by the simultaneous administration of CCl4 and phenobarbital. Hepatic DNA synthesis ([3H]thymidine incorporation into DNA) 24 hr after partial hepatectomy in cirrhotic rats was 15.6 +/- 3.4 cpm/micrograms DNA (means +/- SEM), which was significantly lower than in normal rats (37.3 +/- 3.4 cpm/micrograms DNA, P less than 0.05). Exogenous TGF-alpha (30 nmol/kg, sc every 12 hr) significantly improved [3H]thymidine incorporation (35.6 +/- 8.2 cpm/micrograms DNA, P less than 0.05). An autoradiographic nuclear labeling index also confirmed increased DNA synthesis (6.7% vs 13.4%). TGF-alpha had no effect on normal regenerating liver (42.5 +/- 8.8 cpm/micrograms DNA, NS). Although the significance of TGF-alpha-enhanced liver regeneration in cirrhosis has yet to be assessed, this model may be useful for the study of mechanisms which control hepatic proliferation.
肝硬化时肝脏再生受损使在此情况下发生的肝肿瘤的外科治疗变得复杂。我们建立了一个大鼠模型来研究肝切除术后肝硬化肝脏的再生反应，并研究了外源性转化生长因子-α（TGF-α）的作用，TGF-α是一种有效的肝脏促有丝分裂原。通过同时给予四氯化碳和苯巴比妥建立微结节性肝硬化。肝硬化大鼠部分肝切除术后24小时的肝DNA合成（[3H]胸苷掺入DNA）为15.6±3.4 cpm/μg DNA（均值±标准误），显著低于正常大鼠（37.3±3.4 cpm/μg DNA，P<0.05）。外源性TGF-α（30 nmol/kg，每12小时皮下注射一次）显著改善了[3H]胸苷掺入（35.6±8.2 cpm/μg DNA，P<0.05）。放射自显影核标记指数也证实了DNA合成增加（6.7%对13.4%）。TGF-α对正常再生肝脏无影响（42.5±8.8 cpm/μg DNA，无显著性差异）。虽然TGF-α增强肝硬化肝脏再生的意义尚待评估，但该模型可能有助于研究控制肝脏增殖的机制。
