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用于研究胆道闭锁的慢性肝纤维化小鼠模型。

A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia.

机构信息

School of Medicine, South China University of Technology; Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center.

Provincial Key Laboratory of Research in Structure Birth Defect Disease and Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center.

出版信息

J Vis Exp. 2023 Feb 3(192). doi: 10.3791/65044.

Abstract

Biliary atresia (BA) is a fatal disease involving obstructive jaundice, and it is the most common indication for liver transplantation in children. Due to the complex etiology and unknown pathogenesis, there are still no effective drug treatments. At present, the classic BA mouse model induced by rhesus rotavirus (RRV) is the most commonly used model for studying the pathogenesis of BA. This model is characterized by growth retardation, jaundice of the skin and mucosa, clay stools, and dark yellow urine. The histopathology shows severe liver inflammation and obstruction of the intrahepatic and extrahepatic bile ducts, which are similar to the symptoms of human BA. However, the livers of end-stage mice in this model lack fibrosis and cannot fully simulate the characteristics of liver fibrosis in clinical BA. The presented study developed a novel BA mouse model of chronic liver fibrosis by injecting 5-10 µg of anti-Ly6G antibody four times, with gaps of 2 days after each injection. The results showed that some of the mice successfully formed chronic BA with typical fibrosis after the time lapse, meaning these mice represent a suitable animal model for the virus-induced liver fibrosis mechanistic study of BA and a platform for developing future BA treatments.

摘要

先天性胆道闭锁(BA)是一种致命的疾病,涉及阻塞性黄疸,是儿童肝移植最常见的适应证。由于病因复杂,发病机制不明,目前仍没有有效的药物治疗。目前,恒河猴轮状病毒(RRV)诱导的经典 BA 小鼠模型是研究 BA 发病机制最常用的模型。该模型的特征是生长迟缓、皮肤和黏膜发黄、陶土色粪便和深黄色尿液。组织病理学表现为严重的肝脏炎症和肝内外胆管阻塞,与人类 BA 的症状相似。然而,该模型中终末期小鼠的肝脏缺乏纤维化,无法完全模拟临床 BA 中肝纤维化的特征。本研究通过注射 5-10µg 抗 Ly6G 抗体四次,两次注射间隔 2 天,开发了一种新的慢性肝纤维化 BA 小鼠模型。结果表明,部分小鼠在时间推移后成功形成了具有典型纤维化的慢性 BA,这意味着这些小鼠代表了一种适合 BA 病毒诱导肝纤维化机制研究的动物模型,也是开发未来 BA 治疗方法的平台。

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