硫代乙酰胺
肝细胞癌
肝硬化
内科学
化学
大鼠模型
癌症研究
胃肠病学
医学
作者
Zhiping Hu,Toshio Kurihara,Yiyue Sun,Zeliha Cetin,Rodrigo M. Florentino,Lanuza A.P. Faccioli,Zhenghao Liu,Bo Yang,Alina Ostrowska,Alejandro Soto–Gutiérrez,Evan R. Delgado
标识
DOI:10.1101/2024.04.18.590120
摘要
ABSTRACT Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths, and commonly associated with hepatic fibrosis or cirrhosis. This study aims to establish a rat model mimicking the progression from liver fibrosis to cirrhosis and subsequently to HCC using thioacetamide (TAA). We utilized male Lewis rats, treating them with intra-peritoneal injections of TAA. These rats received bi-weekly injections of either 200 mg/kg TAA or saline (as a control) over a period of 34 weeks. The development of cirrhosis and hepatocarcinogenesis was monitored through histopathological examinations, biochemical markers, and immunohistochemical analyses. Our results demonstrated that chronic TAA administration induced cirrhosis and well-differentiated HCC, characterized by increased fibrosis, altered liver architecture, and enhanced hepatocyte proliferation. Biochemical analyses revealed significant alterations in liver function markers, including elevated alpha-fetoprotein (AFP) levels, without affecting kidney function or causing significant weight loss or mortality in rats. This TAA-induced cirrhosis and HCC rat model successfully replicates the clinical progression of human HCC, including liver function impairment and early-stage liver cancer characteristics. It presents a valuable tool for future research on the mechanisms of antitumor drugs in tumor initiation and development.
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