Liu Tse-Tsung, Shih Kuang-Chung, Kao Chung-Cheng, Cheng Wei-Tung, Hsieh Po-Shiuan
Department of Family and Community, Hualien Army Force Hospital, Hualien, Taiwan, Republic of China.
Chin J Physiol. 2009 Apr 30;52(2):65-71.
This study was designed to examine the role of cyclooxygenase (COX) 2-mediated low-grade inflammation in the development of fructose-induced whole body and muscular insulin resistance in rats. The rats were on regular or fructose-enriched diets for 8 weeks. Fructose-fed rats were further divided into 3 groups (n = 8 per group). There were fructose-fed rats, fructose-fed rats with nimesulide (a selective COX2 inhibitor, 30 mg/kg/day, gavage) and fructose-fed rats with celecoxib (a selective COX2 inhibitor, 30 mg/kg/day, gavage). The present result showed that fructose-induced time-dependent increases in systolic blood pressure and fasting plasma insulin and triglyceride levels were significantly suppressed in rats treated with nimesulide or cerecoxib. The ratio of area under glucose curve divided by area under insulin curve obtained during the oral glucose tolerance test was significantly decreased in fructose-fed rats, which were markedly reversed in those co-treated with nimesulide or celecoxib. Accordingly, fructose-induced decrease in insulin-stimulated glucose uptake in soleus muscle was significantly reversed in those combined with nimesulide or celecoxib. Fructose-induced time-dependent increases in plasma 8-isoprostane and PGE metabolites were concomitantly suppressed by nimesulide or celecoxib co-treatment. The present study demonstrates that the COX2-mediated low-grade inflammation, especially mediated by increase in oxidative stress was important in the development of insulin resistance in fructose-fed rats.
本研究旨在探讨环氧化酶（COX）2介导的低度炎症在果糖诱导的大鼠全身及肌肉胰岛素抵抗发生发展中的作用。大鼠分别给予常规饮食或富含果糖的饮食8周。喂食果糖的大鼠进一步分为3组（每组n = 8）。分别为喂食果糖的大鼠、喂食果糖并给予尼美舒利（一种选择性COX2抑制剂，30毫克/千克/天，灌胃）的大鼠以及喂食果糖并给予塞来昔布（一种选择性COX2抑制剂，30毫克/千克/天，灌胃）的大鼠。目前的结果显示，在给予尼美舒利或塞来昔布治疗的大鼠中，果糖诱导的收缩压、空腹血浆胰岛素和甘油三酯水平随时间的增加得到了显著抑制。在口服葡萄糖耐量试验期间，喂食果糖的大鼠葡萄糖曲线下面积与胰岛素曲线下面积之比显著降低，而在联合使用尼美舒利或塞来昔布治疗的大鼠中，这一比例明显逆转。相应地，在联合使用尼美舒利或塞来昔布的大鼠中，果糖诱导的比目鱼肌胰岛素刺激的葡萄糖摄取减少得到了显著逆转。尼美舒利或塞来昔布联合治疗同时抑制了果糖诱导的血浆8-异前列腺素和前列腺素E代谢产物随时间的增加。本研究表明，COX2介导的低度炎症，尤其是由氧化应激增加介导的炎症，在喂食果糖的大鼠胰岛素抵抗的发生发展中起重要作用。
