Department of Infectious Disease , Third Hospital, Hebei Medical University, Shijiazhuang, China.
Alcohol Clin Exp Res. 2013 Feb;37(2):213-22. doi: 10.1111/j.1530-0277.2012.01936.x. Epub 2012 Sep 25.
To investigate whether "binge" and escalating alcohol exposure in the rat influences the development of pathological liver injury.
Time courses for the formation of eicosanoids by cyclooxygenase (COX), oxidative stress and nitrosative stress production, expression of hypoxia-inducible factor 1 (HIF-1), cytokines, hepatic tissue necroinflammation, and fibrosis were assessed in rats during 16 weeks of daily alcohol gavage.
In this model of binge and escalating levels of alcohol, hepatic steatosis, necrosis, and inflammation as well as fibrosis were increased over the 16-week period. The levels of COX-2, oxidative stress, nitrosative stress, HIF-1, proinflammatory mediators (tumor necrosis factor-α, interleukin 1(β) [IL-1(β) ], IL-6), and procollagen-I were increased over the 16-week period. The content of IL-10 in rat serum increased at the end of 4 and 8 weeks but decreased thereafter and was significantly decreased at 12 and 16 weeks.
A rat model of alcoholic liver disease (ALD) with long-term binge and escalating ethanol exposure was developed. Our data support the hypothesis that enhanced eicosanoid production by COX, oxidative stress and nitrosative stress, HIF-1, and the imbalance between pro- and anti-inflammatory cytokines plays an important role in the pathogenesis of ALD.
为了研究大鼠“狂饮”和不断增加的酒精暴露是否会影响病理性肝损伤的发展。
在大鼠连续 16 周每日酒精灌胃期间，评估环氧合酶（COX）、氧化应激和硝化应激产物、缺氧诱导因子 1（HIF-1）、细胞因子、肝组织坏死性炎症和纤维化形成的时间进程。
在这种“狂饮”和不断增加酒精水平的模型中，肝脂肪变性、坏死和炎症以及纤维化在 16 周的时间内增加。COX-2、氧化应激、硝化应激、HIF-1、促炎介质（肿瘤坏死因子-α、白细胞介素 1β [IL-1β]、白细胞介素 6）和前胶原-I 的水平在 16 周的时间内增加。大鼠血清中 IL-10 的含量在第 4 和 8 周结束时增加，但随后降低，在第 12 和 16 周时显著降低。
建立了一种具有长期“狂饮”和不断增加乙醇暴露的大鼠酒精性肝病（ALD）模型。我们的数据支持这样一种假设，即 COX、氧化应激和硝化应激、HIF-1 产生的类二十烷酸增加以及促炎和抗炎细胞因子之间的失衡在 ALD 的发病机制中起着重要作用。
