Female rats exhibit greater susceptibility to early alcohol-induced liver injury than males
Female rats exhibit greater susceptibility to early alcohol-induced liver injury than males
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DOI：
10.1152/ajpgi.1997.272.5.g1186
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发表时间：
1997-05-01
影响因子：
4.5
通讯作者：
Thurman, RG
中科院分区：
文献类型：
--
作者：
Iimuro, Y;Frankenberg, MV;Thurman, RG
众所周知，与男性相比，女性发生肝损伤的速度更快，且接触的乙醇较少；然而，其机制尚不清楚。本研究的目的是确定肠内酒精给药模型是否可以用于研究女性对酒精性肝损伤的易感性。雄性和雌性Wistar大鼠（年龄或体重匹配）给予11-12 g.kg（-1）乙醇。第(1)天)连续灌胃4周，对照组饲喂不含乙醇的高脂肪饲料。研究小组之间的体重没有显著差异。此外，在这些条件下，平均乙醇浓度、其在尿液中的循环模式和乙醇消除率在性别之间也没有差异。乙醇处理使雄性大鼠血清天冬氨酸转氨酶水平在4周后升高至126 +/- 10 IU/l。然而，在女性中，数值增加得更快，并在第4周达到显著更高的值（168 +/- 18 IU/l）。组织学评估的脂肪变性、炎症和坏死在女性中也比男性发展得更快、更严重。乙醇暴露引起的脂肪变性，在男性中局限于小叶中心区域，在女性中则是全小叶。血浆内毒素含量、肝窦内壁细胞间黏附分子1表达、肝脏浸润炎性细胞数量均为男性的2-2.5倍。这些变化可能解释了乙醇对女性肝损伤的增加。
It is known that women develop hepatic injury more rapidly and with exposure to less ethanol than men; however, mechanisms remain unclear. The purpose of this study was to determine if an enteral alcohol delivery model could be used to study susceptibility of females to alcohol-induced liver injury. Male and female Wistar rats (age- or weight-matched) were given ethanol(11-12 g.kg(-1).day(-1)) continuously for up to 4 wk via intragastric feeding, and control rats received a high-fat diet without ethanol. There were no significant differences in body weight among the groups studied. Furthermore, mean ethanol concentrations, their cyclic pattern in urine, and rates of ethanol elimination were also not different between the genders under these conditions. Ethanol treatment elevated serum aspartate aminotransferase levels in male rats to 126 +/- 10 IU/l after 4 wk. In females, however, values increased more rapidly and reached significantly higher values at 4 wk (168 +/- 18 IU/l). Steatosis, inflammation, and necrosis assessed histologically also developed more rapidly and were more severe in females than males. Steatosis due to ethanol exposure, which was localized in centrilobular areas in males, was panlobular in the female. Moreover, endotoxin in plasma, intercellular adhesion molecule 1 expression in hepatic sinusoidal-lining cells, and the number of infiltrating inflammatory cells in the liver were 2-2.5-fold greater in females than males. These changes possibly account for increased hepatic injury due to ethanol in the female.