Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance
Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance
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DOI：
10.1155/2010/312790
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发表时间：
2010-01-01
影响因子：
2
通讯作者：
de la Monte, Suzanne M.
中科院分区：
文献类型：
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作者：
DeNucci, Sarah M.;Tong, Ming;de la Monte, Suzanne M.
与Sprague道利（SD）和Fisher 344（FS）大鼠相比，在酒精喂养的Long Evans（LE）大鼠中发现更严重的脂肪性肝炎，这促使我们确定与酒精代谢、炎症和胰岛素/IGF信号相关的宿主因素是否可预测酒精介导的肝损伤倾向。成年FS、SD和LE大鼠饲喂含0%或37%（卡路里）乙醇的流质饲料8周。在对照组中，LE大鼠相对于SD和FS大鼠具有显著更高的ALT和降低的GAPDH。在乙醇喂养的大鼠中，尽管血液酒精水平相似，但LE大鼠的脂肪性肝炎和纤维化更明显，ALT、DNA损伤、促炎细胞因子、ADH、ALDH、过氧化氢酶、GFAP、结蛋白和胶原蛋白表达水平更高，胰岛素受体结合相对于FS大鼠降低。乙醇暴露的SD大鼠有中等程度的脂肪性肝炎，ALT，ADH和促纤维化基因表达增加，抑制胰岛素受体结合和GAPDH表达，而促炎细胞因子类似地增加，在LE大鼠。酒精喂养FS大鼠只减少IL-6，ALDH 1 -3，CYP 2 E1，和GAPDH在肝脏中的表达。总之，慢性脂肪性肝炎的易感性可能与乙醇代谢效率和乙醇暴露导致肝胰岛素抵抗和细胞因子激活的程度相关。
The finding of more severe steatohepatitis in alcohol fed Long Evans (LE) compared with Sprague Dawley (SD) and Fisher 344 (FS) rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories) ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1-3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.