Reevaluation of Experimental Model of Hepatic Fibrosis Induced by Hepatotoxic Drugs: An Easy, Applicable, and Reproducible Model
Reevaluation of Experimental Model of Hepatic Fibrosis Induced by Hepatotoxic Drugs: An Easy, Applicable, and Reproducible Model
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DOI：
10.1016/j.transproceed.2008.07.040
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发表时间：
2008-10-01
影响因子：
0.9
通讯作者：
Lee, I. S.
中科院分区：
文献类型：
--
作者：
Jang, J. H.;Kang, K. J.;Lee, I. S.
建立一种简单易行、重复性好的肝纤维化模型是研究肝脏再灌注损伤的必要条件。我们比较了几种肝硬化模型在纤维化程度、可重复性、组织学特征和成功率方面的特点，以达到足够的纤维化。在小鼠和大鼠中，我们通过两种不同的途径（口服和腹腔注射）给予三种不同的肝毒性药物（硫代乙酰胺，二甲基亚硝胺和四氯化碳[CCl 4]）。喂食硫代乙酰胺的动物表现出很少的纤维化;相反，更多的炎性细胞浸润到门静脉周围区域并伴有胆管增生。给予二甲基亚硝胺的宿主的肝脏表现出更大的早期损伤和严重的腹腔炎症反应。肝脏显示出明显程度的碎片状坏死伴有限的纤维化。给予50% CCl 4溶液（2 mL/kg口服）的小鼠耐受了12周的整个诱导期。纤维化程度与诱导时间密切相关。每周两次口服CCl 4，持续10周的宿主肝脏最有效地实现了足够的纤维化和最大的可重复性，动物存活率可接受。
Establishing an easy and reproducible model for hepatic fibrosis is absolutely necessary for research on liver reperfusion injury. We compared the characteristics of several hepatic cirrhosis models in terms of the degree of fibrosis, reproducibility, histologic characteristics, and success rate to achieve sufficient fibrosis. In mice & rats, we administered three different hepatotoxic drugs (thioacetamide, dimethylnitrosamine, and carbon tetrachloride [CCl4]) through two different routes (oral feeding and intraperitoneal injection). The animals fed thioacetamide exhibited little fibrosis; rather, more inflammatory cells infiltrated into periportal areas with bile duct proliferation. The livers from hosts administered dimethylnitrosamine showed greater early injury and severe inflammatory reactions in the peritoneal cavity. The liver showed a marked degree of piecemeal necrosis with limited fibrosis. The mice administered a 50% solution of CCl4 (2 mL/kg orally) tolerated the entire induction period of 12 weeks. The degree of fibrosis correlated well with the duration of induction. Livers from hosts administered CCl4 orally twice a week for 10 weeks was the most effective to achieve sufficient fibrosis and greatest reproducibility with acceptable animal survival.