Wallace M C, Hamesch K, Lunova M, Kim Y, Weiskirchen R, Strnad P, Friedman S L
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Internal Medicine III, RWTH University Hospital Aachen, Aachen, Germany.
Lab Anim. 2015 Apr;49(1 Suppl):21-9. doi: 10.1177/0023677215573040.
In addition to carbon tetrachloride (CCl4), thioacetamide (TAA) represents a second widely used model for the induction of experimental liver fibrosis, but can also be employed for the development of acute liver failure and liver tumours. While TAA itself is not hepatotoxic, its reactive metabolites covalently bind to proteins and lipids thereby causing oxidative stress and centrilobular necrosis. Compared with CCl4, TAA leads to more periportal infiltrates and more pronounced ductal proliferation. While TAA has been shown to induce liver fibrosis development in several different mouse strains, wide variations in the administration routes, doses and treatment durations have been reported. Therefore, an adoption of a universal standard operating procedure for the administration of TAA is urgently needed. For that purpose, we are presenting here two TAA models (intraperitoneal administration of 150 mg/kg of TAA three times per week for 11 weeks in rats, and TAA administration in drinking water at 300 mg/L for 2-4 months in mice) with which we have had success in reliably and reproducibly developing chronic liver injury and fibrosis.
除四氯化碳（CCl4）外，硫代乙酰胺（TAA）是另一种广泛用于诱导实验性肝纤维化的模型，也可用于急性肝衰竭和肝肿瘤的研究。虽然TAA本身没有肝毒性，但其活性代谢产物会与蛋白质和脂质共价结合，从而导致氧化应激和小叶中心坏死。与CCl4相比，TAA会导致更多的门周浸润和更明显的导管增生。虽然已证明TAA能在几种不同的小鼠品系中诱导肝纤维化发展，但报道的给药途径、剂量和治疗持续时间存在很大差异。因此，迫切需要采用通用的TAA给药标准操作规程。为此，我们在此介绍两种TAA模型（大鼠每周腹腔注射150 mg/kg TAA，共3次，持续11周；小鼠饮用含300 mg/L TAA的水，持续2 - 4个月），我们已成功地利用这两种模型可靠且可重复地诱导慢性肝损伤和纤维化。
