PDF(Pubmed)
Abstract：
Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by intense deposition of fat globules in the hepatic parenchyma that could potentially progress to liver cirrhosis and hepatocellular carcinoma. Here, we evaluated a rat model to study the molecular pathogenesis of the spectrum of MASLD and to screen therapeutic agents. SHRSP5/Dmcr rats were fed a high-fat and cholesterol (HFC) diet for a period of 12 weeks and evaluated for the development of steatosis (MASLD), steatohepatitis, fibrosis and cirrhosis. A group of animals were sacrificed at the end of the 4th, 6th, 8th and 12th weeks from the beginning of the experiment, along with the control rats that received normal diet. Blood and liver samples were collected for biochemical and histopathological evaluations. Immunohistochemical staining was performed for α-SMA and Collagen Type I. Histopathological examinations demonstrated steatosis at the 4th week, steatohepatitis with progressive fibrosis at the 6th week, advanced fibrosis with bridging at the 8th week and cirrhosis at the 12th week. Biochemical markers and staining for α-SMA and Collagen Type I demonstrated the progression of steatosis to steatohepatitis, hepatic fibrosis and liver cirrhosis in a stepwise manner. Control animals fed a normal diet did not show any biochemical or histopathological alterations. The results of the present study clearly demonstrated that the HFC diet-induced model of steatosis, steatohepatitis, hepatic fibrosis and cirrhosis is a feasible, quick and appropriate animal model to study the molecular pathogenesis of the spectrum of MASLD and to screen potent therapeutic agents.
摘要：
代谢功能障碍相关的脂肪变性肝病（MASLD）的特征是肝实质中脂肪球的大量沉积，可能会进展为肝硬化和肝细胞癌。这里,我们评估了一个大鼠模型，以研究MASLD谱的分子发病机制并筛选治疗药物。SHRSP5/Dmcr大鼠喂食高脂肪和胆固醇（HFC）饮食12周，并评估脂肪变性（MASLD）的发展，脂肪性肝炎,纤维化和肝硬化。一组动物在4号结束时被处死，6th,实验开始的第8周和第12周，以及接受正常饮食的对照大鼠。收集血液和肝脏样品用于生化和组织病理学评估。对α-SMA和I型胶原进行免疫组织化学染色。组织病理学检查在第4周显示脂肪变性，在第6周伴有进行性纤维化的脂肪性肝炎，晚期纤维化与桥接在第8周和肝硬化在第12周。生化标记和染色α-SMA和I型胶原证明了脂肪变性进展为脂肪性肝炎，肝纤维化和肝硬化的逐步方式。饲喂正常饮食的对照动物没有显示任何生化或组织病理学改变。本研究的结果清楚地表明，HFC饮食诱导的脂肪变性模型，脂肪性肝炎,肝纤维化和肝硬化是可行的，快速和适当的动物模型，以研究MASLD谱的分子发病机理并筛选有效的治疗剂。
