Rozga J, Foss A, Alumets J, Ahren B, Jeppsson B, Bengmark S
Department of Surgery, University of Lund, Sweden.
J Surg Res. 1991 Oct;51(4):329-35. doi: 10.1016/0022-4804(91)90116-4.
A common model for producing experimental liver cirrhosis is the administration of CCl4 to phenobarbital (PhB)-stimulated rats. However, concern may arise due to the complex actions of PhB upon liver metabolism. This study examined the role of PhB in the production of CCl4-induced liver cirrhosis in the rat. In addition, regenerative capacity of the liver after partial hepatectomy (PH) or portal branch ligation (PBL) was studied in cirrhotic rats, rats treated with CCl4 alone, and in PhB-treated controls. In rats given PhB throughout the CCl4-induction period, ascitic form of micronodular cirrhosis was found in 93% with only 3% mortality. In contrast, rats pretreated with PhB for only 2 weeks followed by CCl4 alone for 18 weeks did not develop liver cirrhosis. In most of the cirrhotic rats, PH induced hepatic regeneration associated with improved liver histology. PBL was less effective. Treatment with PhB alone for 10 weeks resulted in liver atrophy and reduced hepatic regenerative capacity. Impaired regeneration response was also found in rats treated with CCl4 alone. In conclusion, treatment with PhB throughout the CCl4-induction period seems necessary for the production of liver cirrhosis in rats. However, prolonged treatment with PhB alone results in liver atrophy and an impaired regenerative response. Therefore, though necessary for the cirrhotic model, PhB by itself has negative hepatotrophic influences which questions the thoroughness of the PhB/CCl4 experimental model.
一种常见的用于产生实验性肝硬化的模型是给苯巴比妥（PhB）刺激的大鼠注射四氯化碳（CCl4）。然而，由于PhB对肝脏代谢的复杂作用，可能会引发担忧。本研究探讨了PhB在大鼠CCl4诱导的肝硬化形成过程中的作用。此外，还研究了肝硬化大鼠、仅接受CCl4处理的大鼠以及接受PhB处理的对照大鼠在部分肝切除（PH）或门静脉分支结扎（PBL）后肝脏的再生能力。在整个CCl4诱导期给予PhB的大鼠中，93%出现了腹水型小结节性肝硬化，死亡率仅为3%。相比之下，仅用PhB预处理2周，随后单独给予CCl4 18周的大鼠未发生肝硬化。在大多数肝硬化大鼠中，PH诱导了肝脏再生，肝脏组织学得到改善。PBL的效果较差。单独用PhB处理10周导致肝脏萎缩，肝脏再生能力降低。在仅接受CCl4处理的大鼠中也发现再生反应受损。总之，在整个CCl4诱导期用PhB处理似乎是大鼠产生肝硬化所必需的。然而，单独长期使用PhB会导致肝脏萎缩和再生反应受损。因此，尽管PhB对肝硬化模型是必需的，但其本身具有负面的肝营养影响，这对PhB/CCl4实验模型的完整性提出了质疑。
