Lijnen H Roger, Van Hoef Berthe, Lu Hua Rong, Gallacher David J
Center for Molecular and Vascular Biology, KU Leuven, Campus Gasthuisberg, O & N 1, Leuven, Belgium.
Thromb Haemost. 2008 Aug;100(2):338-42.
The effect of rofecoxib (Vioxx), a cyclooxygenase (COX)-2 inhibitor, on adipose tissue development was studied in a murine model of diet-induced obesity. Oral administration of Vioxx for six weeks (34 mg/kg/day) to C57Bl/6 mice kept on high-fat diet (n = 19) resulted in a significant reduction in total body weight (p < 0.01) and of subcutaneous (p < 0.05) and gonadal (p < 0.01) adipose tissue mass, as compared to placebo-treated animals (n = 21). There was no significant difference in food intake between both groups (2.8 +/- 0.09 vs. 3.0 +/- 0.10 g/day; p = 0.20). Administration of Vioxx resulted in reduced total cholesterol and high-density lipoprotein (HDL) cholesterol levels (p < 0.0001) and in enhanced levels of liver enzymes, as compared to place-bo. In the gonadal but not in the subcutaneous adipose tissue, adipocytes were smaller after Vioxx treatment (p < 0.05). The macrophage content was significantly lower in gonadal adipose tissues of Vioxx-treated mice (p < 0.05), but not in the subcutaneous adipose tissues. This was, however, not associated with differences in adipose tissue levels of the pro-inflammatory tumor necrosis factor (TNF)-alpha. Blood vessel size or density in either fat pad were not affected by Vioxx treatment. Thus, in a nutritionally induced murine obesity model, oral administration of Vioxx, as compared to placebo, resulted in reduced adipose tissue development, associated with lower feeding efficiency and smaller adipocytes.
在饮食诱导肥胖的小鼠模型中，研究了环氧化酶（COX）-2抑制剂罗非昔布（万络）对脂肪组织发育的影响。给高脂饮食的C57Bl/6小鼠（n = 19）口服万络六周（34毫克/千克/天），与给予安慰剂的动物（n = 21）相比，体重显著降低（p < 0.01），皮下脂肪组织（p < 0.05）和性腺脂肪组织（p < 0.01）质量也显著降低。两组之间的食物摄入量没有显著差异（2.8±0.09对3.0±0.10克/天；p = 0.20）。与给予安慰剂相比，给予万络导致总胆固醇和高密度脂蛋白（HDL）胆固醇水平降低（p < 0.0001），肝酶水平升高。在性腺脂肪组织而非皮下脂肪组织中，万络治疗后脂肪细胞较小（p < 0.05）。万络治疗小鼠的性腺脂肪组织中巨噬细胞含量显著较低（p < 0.05），但皮下脂肪组织中没有。然而，这与促炎肿瘤坏死因子（TNF）-α的脂肪组织水平差异无关。万络治疗对任何一个脂肪垫中的血管大小或密度均无影响。因此，在营养诱导的小鼠肥胖模型中，与安慰剂相比，口服万络导致脂肪组织发育减少，伴有较低的喂养效率和较小的脂肪细胞。
