一种慢性肝衰竭大鼠动物模型的制备方法研究
Preparation of a rat model of chronic liver failure
摘要
Abstract
Objective To prepare a stable rat model of chronic liver failure to provide a tool for basic research.Methods Sixty-six SPF SD rats were divided into a normal group(n=18)and a modeling group(n=48).Rats in the modeling group received an intraperitoneal injection of 50％CCl4 olive oil solution(1.5 mL/kg,twice a week).Multidimensional assessment was performed at 8,16,and 24 weeks,respectively,including ultrasonic examination of liver morphology,hardness,portal vein diameter,and ascites,and collection of serum,plasma,and liver tissue to detect liver function,coagulation function,and blood ammonia levels.Liver tissue injury and fibrosis were observed by hematoxylin-eosin(HE)and Masson staining.Cognitive function was assessed using the water maze test.Survival were recorded simultaneously.Results Rats in the model group showed decreased activity and appetite,yellow urine,and increased abdominal circumference compared with the normal group.Ultrasound showed enhanced liver parenchyma echo in the model group that thickened with time,secondary ascites formation,portal vein dilation,and portal hypertension.Water maze and blood ammonia tests confirmed cognitive decline(memory and orientation loss)and hepatic encephalopathy in the model group.Gross observation showed that the liver in the model group was atrophied and appeared rough and uneven.HE staining showed hepatocyte swelling,steatosis,and necrosis,and Masson staining confirmed fibrosis progression with pseudolobule formation.The liver function indexes AST,ALT,TBIL and blood ammonia continued to increase,and coagulation dysfunction(prolonged PT and increased INR)gradually increased with the modeling process.Conclusions Intraperitoneal injection of 50％CCl4 olive oil solution(1.5 mL/kg,every week)for 24 weeks can stably simulate persistent chronic liver injury in rats and lead to the typical pathological changes and complications of chronic liver failure,based on the decompensation stage of cirrhosis.This model replicates the pathological evolution of human hepatitis from liver fibrosis → liver cirrhosis compensation → decompensation → chronic liver failure,providing a reliable modeling reference for the study of the mechanism of chronic liver failure.关键词
慢性肝衰竭/四氯化碳/动物模型/大鼠Key words
chronic liver failure/carbon tetrachloride/animal model/rat分类
生物科学引用本文复制引用
王娜,舒发明,蓝艳梅,毛德文,陆正峰,王明刚,吴凤兰,张日云,张荣臻,冯雯倩,刘好,杜洋..一种慢性肝衰竭大鼠动物模型的制备方法研究[J].中国实验动物学报,2025,33(6):811-822,12.基金项目
广西重点研发计划项目(桂科AB25069020),广西自然科学基金(2023GXNSFAA026176,2024GXNSFBA010218,2021GXNSFAA220112),国家中医药传承创新中心建设项目(发改办社会[2022]366号),国家自然科学基金(82274434,82360912,82160881),广西高校中青年教师科研基础能力提升项目(2024ky0123) （桂科AB25069020）
广西壮族自治区民族医院孵化项目(民科FY202404),广西中药大学青年基金项目(2023QN007),广西中药大学第一附属医院青年基金项目(2022QN009).Funded by Guangxi Key Research and Development Program Project(Guike AB25069020),Guangxi Natural Science Foundation(2023GXNSFAA026176,2024GXNSFBA010218,2021GXNSFAA220112),Construction Project of the National Traditional Chinese Medicine Inheritance and Innovation Center(Document No.[2022]366 of the Office of the National National Development and Reform Commission in Social Affairs),National Natural Science Foundation of China(82274434,82360912,82160881),Guangxi University Young and Middle-Aged Teachers Research Basic Ability Improvement Project(2024ky0123),Guangxi Zhuang Autonomous Region Ethnic Hospital Incubation Project(MingkeFY202404),Guangxi University of Chinese Medicine Youth Fund Project(2023QN007),Youth Fund Project of the First Affiliated Hospital of Guangxi University of Chinese Medicine(2022QN009). （民科FY202404）
