使用交叉高酒精偏好 (cHAP) 小鼠模型和 NIAAA 模型来研究肝损伤。,Alcohol and Alcoholism

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使用交叉高酒精偏好 (cHAP) 小鼠模型和 NIAAA 模型来研究肝损伤。
Alcohol and Alcoholism ( IF 2.1 ) Pub Date : 2017-11-01 , DOI: 10.1093/alcalc/agx063
Kyle J Thompson ₁ , Shayan S Nazari _{1,

2} , W Carl Jacobs ₃ , Nicholas J Grahame ₄ , Iain H McKillop ₁

Affiliation

目的本研究试图比较使用慢性酒精摄入模型诱发酒精性肝病 (ALD) 的小鼠与 c57BL/6 (C57) 小鼠相比，这些小鼠优先消耗大量酒精（交叉高酒精偏好，cHAP）。方法雄性 C57 和 cHAP 小鼠被随机分配到 Lieber-DeCarli 对照 (LDC) 饮食、Lieber-DeCarli 5% (v/v) 乙醇 (LDE) 饮食或饮用水中 10% (v/v) 乙醇的自由选择(EtOH-DW) 和 DW。4 周后，用 9 g/kg 麦芽糖糊精 (LDC+MD) 或 5 g/kg EtOH (LDE+Binge，EtOH-DW+Binge) 对小鼠进行管饲。九小时后收集和分析组织和血清。结果使用 EtOH-DW 的 cHAP 小鼠比使用 LDE 的 cHAP 或 C57 小鼠消耗的乙醇显着更多。然而，与 EtOH-DW+Binge 相比，LDE+Binge 组的 cHAP 和 C57 小鼠肝脂肪变性和总体肝损伤程度更大。促炎基因表达的变化在 cHAP 小鼠中比 C57 小鼠更明显。肝酶分析显示，在维持 EtOH-DW+Binge 或 LDE+Binge 的 C57 和 cHAP 小鼠中强烈诱导 CYP2E1。然而，虽然 C57 小鼠比 cHAP 小鼠表现出更高的基础肝谷胱甘肽，但这些小鼠在 LDE+Binge 后似乎比 cHAP 小鼠更容易受到氧化应激的影响。结论尽管当维持在 EtOH-DW 上时，cHAP 小鼠在灌胃前消耗了更多的总乙醇，LDE 然后灌胃在 C57 和 cHAP 小鼠中产生了更严重的 ALD 模型。这些数据表明，除了饮酒总量之外的因素会影响 cHAP 小鼠慢性暴饮暴食模型中 ALD 发展的程度。简短摘要 cHAP 小鼠自愿消耗大量乙醇，并在长期以 Lieber-DeCarli 饮食进行过量乙醇喂养时表现出肝损伤。然而，在慢性暴饮暴食模型中，在饮用水中自愿消耗大量乙醇后，cHAP 小鼠的肝损伤有所减轻。

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Use of a crossed high alcohol preferring (cHAP) mouse model with the NIAAA-model of chronic-binge ethanol intake to study liver injury.

AIMS This study sought to compare mice bred to preferentially consume high amounts of alcohol (crossed-high alcohol preferring, cHAP) to c57BL/6 (C57) mice using a chronic-binge ethanol ingestion model to induce alcoholic liver disease (ALD). METHODS Male C57 and cHAP mice were randomized to a Lieber-DeCarli control (LDC) diet, Lieber-DeCarli 5% (v/v) ethanol (LDE) diet or free-choice between 10% (v/v) ethanol in drinking water (EtOH-DW) and DW. After 4 weeks mice were gavaged with either 9 g/kg maltose-dextrin (LDC+MD) or 5 g/kg EtOH (LDE+Binge, EtOH-DW+Binge). Nine hours later tissue and serum were collected and analyzed. RESULTS cHAP mice on EtOH-DW consumed significantly more ethanol than cHAP or C57 mice maintained on LDE. However, cHAP and C57 mice on the LDE+Binge regiment had greater hepatosteatosis and overall degree of liver injury compared to EtOH-DW+Binge. Changes in pro-inflammatory gene expression was more pronounced in cHAP mice than C57 mice. Analysis of liver enzymes revealed a robust induction of CYP2E1 in C57 and cHAP mice maintained on EtOH-DW+Binge or LDE+Binge. However, while C57 mice exhibited higher basal hepatic glutathione than cHAP mice, these mice appeared more susceptible to oxidative stress following LDE+Binge than cHAP counterparts. CONCLUSIONS Despite cHAP mice consuming more total ethanol prior to gavage when maintained on EtOH-DW, LDE followed by gavage created a more severe model of ALD in both C57 and cHAP mice. These data suggest factors other than total amount of alcohol consumed affect degree of ALD development in the chronic-binge model in cHAP mice. SHORT SUMMARY cHAP mice voluntarily consume high amounts of ethanol and exhibited hepatic injury when subject to chronic-binge ethanol feeding with the Lieber-DeCarli diet. However, hepatic injury was reduced in cHAP mice in a chronic-binge model following voluntary high ethanol consumption in drinking water.

更新日期：2019-11-01

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