Akimoto Toshio, Hayashi Norihide, Adachi Mari, Kobayashi Nobuaki, Zhang Xue-Jun, Ohsuga Masaru, Katsuta Yasumi
Division of Laboratory Animal Science, Nippon Medical School, Tokyo, Japan.
Exp Anim. 2005 Apr;54(2):155-61. doi: 10.1538/expanim.54.155.
The common bile duct-ligated (CBDL) rat, which is widely used as a model of human cirrhosis, rapidly develops secondary biliary cirrhosis (SBC) within 4 weeks. The CBDL rat shows poor viability, however, a detailed examination of the causes of its death has not been made. In this study, we investigated the outcome of bile duct ligation in detail and attempted to extend the life span of this model by feeding the animals a diet supplemented with nutrients. Survival rate, blood chemistry, blood cell counts, plasma levels of K vitamins and liver histology were compared among CBDL rats fed a standard diet and an enriched diet. Sham-operated rats were used as a control. Six out of 18 CBDL rats fed the standard diet died within 32 days of operation. The cause of death was massive internal hemorrhage in various organs or body cavities. All CBDL rats fed the enriched diet survived more than 31 days, but the viability of CBDL rats was not significant between those fed the standard diet and the enriched diet. The degree of anemia correlated significantly with the prolongation of prothrombin time. Plasma vitamin K1 levels in CBDL rats were significantly lower than those in sham-operated rats, but vitamin K2 levels were similar. We suggest that massive hemorrhage, which was the direct cause of death, is caused by the impairment of hemostasis resulting from vitamin K deficiency. The enriched diet with vitamin K nutritional supplements seemed to contribute to the prolongation of the life span of CBDL rats.
胆总管结扎(CBDL)大鼠被广泛用作人类肝硬化模型,在4周内会迅速发展为继发性胆汁性肝硬化(SBC)。然而,CBDL大鼠的生存能力较差,尚未对其死亡原因进行详细检查。在本研究中,我们详细调查了胆管结扎的结果,并试图通过给动物喂食补充营养的饮食来延长该模型的寿命。比较了喂食标准饮食和强化饮食的CBDL大鼠的存活率、血液化学指标、血细胞计数、血浆K族维生素水平和肝脏组织学。假手术大鼠用作对照。喂食标准饮食的18只CBDL大鼠中有6只在手术后32天内死亡。死亡原因是各个器官或体腔大量内出血。所有喂食强化饮食的CBDL大鼠存活超过31天,但喂食标准饮食和强化饮食的CBDL大鼠的生存能力没有显著差异。贫血程度与凝血酶原时间延长显著相关。CBDL大鼠的血浆维生素K1水平显著低于假手术大鼠,但维生素K2水平相似。我们认为,作为直接死亡原因的大量出血是由维生素K缺乏导致的止血功能受损引起的。富含维生素K营养补充剂的强化饮食似乎有助于延长CBDL大鼠的寿命。