重症酒精性肝炎小鼠模型的建立与评价  

Establishment and evaluation of a mouse model of severe alcoholic hepatitis

作　　者：朱学进 郑淑文 周光德 许燕瑜 潘涛 刘敏[2,4] 王伽伯[1,2,4] 王英豪 ZHU Xue-jin;ZHENG Shu-wen;ZHOU Guang-de;XU Yan-yu;PAN Tao;LIU Min;WANG Jia-bo;WANG Ying-hao(School of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;College of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China;Clinical Pathology Center of Beijing You'an Hospital,Capital Medical University,Beijing 100069,China;Research and Translational Laboratory for Traditional Chinese Medicine in the Prevention and Treatment of Infectious Severe Hepatitis,Capital Medical University,Beijing 100069,China)

机构地区：[1]福建中医药大学药学院,福建福州350122 [2]首都医科大学中医药学院,北京100069 [3]首都医科大学附属北京佑安医院临床病理中心,北京100069 [4]首都医科大学中医药防治传染性重症肝病研究与转化实验室,北京100069

出　　处：《药学学报》2025年第4期1029-1040,共12页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金联合基金重点支持项目(U21A200211);“国家资助博士后研究人员计划”资助(GZC20231759)。

摘　　要：重症酒精性肝炎(severe alcoholic hepatitis,SAH)是酒精性肝病中最严重的一种,死亡率极高,目前缺乏适合的动物模型进行相关研究。本研究旨在建立一种小鼠SAH模型为后续开展重症酒精性肝炎的相关研究提供临床前动物模型。本研究在NIAAA(National Institute on Alcohol Abuse and Alcoholism)模型的基础上采用联合给予细菌内毒素构建小鼠模型[本实验所有动物实验均获得首都医科大学动物伦理委员会批准,批准号:AEEI-2023-102]。在小鼠死亡率、肝脏组织损伤及炎症相关指标等方面模拟临床重症酒精性肝炎的病理过程。最终确立在NIAAA模型的基础上,最后一次灌胃酒精浓度为7.5 g·kg^(-1),联合腹腔注射脂多糖剂量5 mg·kg^(-1),作用时间12 h作为SAH小鼠造模最优条件。该条件下,小鼠模型能够较好地模拟临床上SAH的高死亡率、肝脏功能损害,并且其病理染色结果与临床结果高度一致,肝脏中也出现了大量中性粒细胞浸润等过度炎症反应的情况,为SAH的临床前研究提供了理想的模型。Severe alcoholic hepatitis(SAH) represents the most extreme form of alcoholic liver disease(ALD),accompanied by an extremely high mortality rate.Currently,there is a dearth of appropriate animal models for related research.The objective of this study is to establish a mouse model of SAH,thereby providing a preclinical animal model for subsequent research on SAH.This study is based on the NIAAA(National Institute on Alcohol Abuse and Alcoholism) model and constructs a mouse model by combining bacterial endotoxins.This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University(approval number:AEEI-2023-102).The model emulates the pathological processes of clinical SAH in terms of mouse mortality,liver tissue damage,and inflammatory markers,thereby establishing the model.Ultimately,it is ascertained that the optimal conditions for SAH mouse modeling based on the NIAAA model are the last intragastric administration of alcohol at a concentration of 7.5 g·kg-1 in combination with intraperitoneal injection of lipopolysaccharide at a dose of 5 mg·kg-1 for a period of 12 h.Under these conditions,the mouse model effectively simulates the high mortality and liver dysfunction seen in clinical SAH,with pathological staining results closely mirroring clinical findings.Additionally,it demonstrates a significant infiltration of neutrophils in the liver,indicative of an excessive inflammatory response.This model provides an ideal platform for preclinical research on SAH.

关 键 词：重症酒精性肝炎 肝损伤 炎症反应 动物模型 模型评价 

分 类 号：R965.1[医药卫生—药理学]