Kashireddy Pap Reddy V, Rao M Sambasiva
Department of Pathology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Exp Biol Med (Maywood). 2004 Feb;229(2):158-62. doi: 10.1177/153537020422900204.
Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are common liver diseases in the United States. ASH and NASH occur more frequently in women than in men, and liver injury is also more severe in women. The role of estrogens in ASH has been well established, but their role in NASH has received relatively little study. The purpose of this study was to evaluate the effect of estrogens in methionine-choline deficient diet (MCDD)-induced steatohepatitis in mice. The degree of steatohepatitis was evaluated in males and in intact and ovariectomized females that were fed MCDD for 4 weeks, and in females that were fed MCDD containing tamoxifen. Hematoxylin and eosin-stained sections of livers showed marked steatohepatitis in all experimental groups. Compared to the control group, markers of hepatocyte injury such as aspartate transaminase (AST), alanine transaminase (ALT), and liver triglyceride levels increased significantly in males and in intact and ovariectomized female mice that were fed MCDD. Also, it was interesting that levels of AST and ALT increased much more in the MCDD + tamoxifen group than in the MCDD group. In female mice fed MCDD, hepatocyte proliferative and apoptotic indices increased slightly compared to mice that were fed a normal diet. Based on these results, it can be concluded that MCDD-induced steatohepatitis is comparable in male and female mice, and that ovariectomy or antiestrogen treatment had no protective effect in MCDD-induced steatohepatitis.
酒精性脂肪性肝炎（ASH）和非酒精性脂肪性肝炎（NASH）是美国常见的肝脏疾病。ASH和NASH在女性中比在男性中更频繁发生，并且女性的肝损伤也更严重。雌激素在ASH中的作用已得到充分证实，但其在NASH中的作用相对研究较少。本研究的目的是评估雌激素对蛋氨酸 - 胆碱缺乏饮食（MCDD）诱导的小鼠脂肪性肝炎的影响。对喂食MCDD 4周的雄性、完整雌性和去卵巢雌性小鼠以及喂食含他莫昔芬的MCDD的雌性小鼠的脂肪性肝炎程度进行评估。苏木精和伊红染色的肝脏切片显示所有实验组均有明显的脂肪性肝炎。与对照组相比，喂食MCDD的雄性、完整雌性和去卵巢雌性小鼠中，肝细胞损伤标志物如天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）和肝脏甘油三酯水平显著升高。此外，有趣的是，MCDD +他莫昔芬组中AST和ALT的水平比MCDD组升高得更多。在喂食MCDD的雌性小鼠中，与喂食正常饮食的小鼠相比，肝细胞增殖和凋亡指数略有增加。基于这些结果，可以得出结论，MCDD诱导的脂肪性肝炎在雄性和雌性小鼠中相当，并且去卵巢或抗雌激素治疗对MCDD诱导的脂肪性肝炎没有保护作用。
