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建立具有模拟人类饮酒模式和低剂量化学刺激的酒精性肝纤维化大鼠模型。

Establishment of a Rat Model of Alcoholic Liver Fibrosis with Simulated Human Drinking Patterns and Low-Dose Chemical Stimulation.

作者信息

Lin Chien-Yu, Omoscharka Evanthia, Liu Yanli, Cheng Kun

机构信息

Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, MO 64108, USA.

Department of Pathology, University Health/Truman Medical Center, School of Medicine, University of Missouri-Kansas City, 2301 Holmes Street, Kansas City, MO 64108, USA.

出版信息

Biomolecules. 2023 Aug 24;13(9):1293. doi: 10.3390/biom13091293.

Abstract

Although alcohol is a well-known causal factor associated with liver diseases, challenges remain in inducing liver fibrosis in experimental rodent models. These challenges include rodents' natural aversion to high concentrations of alcohol, rapid alcohol metabolism, the need for a prolonged duration of alcohol administration, and technical difficulties. Therefore, it is crucial to establish an experimental model that can replicate the features of alcoholic liver fibrosis. The objective of this study was to develop a feasible rat model of alcoholic liver fibrosis that emulates human drinking patterns and combines low-dose chemicals within a relatively short time frame. We successfully developed an 8-week rat model of alcoholic liver fibrosis that mimics chronic and heavy drinking patterns. Rats were fed with a control liquid diet, an alcohol liquid diet, or alcohol liquid diet combined with multiple binges via oral gavage. To accelerate the progression of alcoholic liver fibrosis, we introduced low-dose carbon tetrachloride (CCl) through intraperitoneal injection. This model allows researchers to efficiently evaluate potential therapeutics in preclinical studies of alcoholic liver fibrosis within a reasonable time frame.

摘要

尽管酒精是与肝脏疾病相关的一个众所周知的致病因素,但在实验啮齿动物模型中诱导肝纤维化仍存在挑战。这些挑战包括啮齿动物对高浓度酒精的天然厌恶、酒精代谢迅速、需要长时间给予酒精以及技术难题。因此,建立一个能够复制酒精性肝纤维化特征的实验模型至关重要。本研究的目的是开发一种可行的酒精性肝纤维化大鼠模型,该模型模拟人类饮酒模式,并在相对较短的时间内结合低剂量化学物质。我们成功开发了一种为期8周的酒精性肝纤维化大鼠模型,该模型模拟慢性重度饮酒模式。通过口服灌胃给大鼠喂食对照液体饮食、酒精液体饮食或多次暴饮结合酒精液体饮食。为了加速酒精性肝纤维化的进展,我们通过腹腔注射引入低剂量四氯化碳(CCl)。该模型使研究人员能够在合理的时间范围内,在酒精性肝纤维化的临床前研究中有效评估潜在的治疗方法。

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