Establishment and evaluation of a mouse model of severe alcoholic hepatitis

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.