Dinh Chi H L, Yu Yinghua, Szabo Alexander, Zhang Qingsheng, Zhang Peng, Huang Xu-Feng
Centre for Translational Neuroscience, School of Medicine, University of Wollongong and Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia (CHLD, YY, AS, QZ, XH)
ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, Australia (AS)
J Histochem Cytochem. 2016 Apr;64(4):237-55. doi: 10.1369/0022155416631803. Epub 2016 Feb 26.
Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora.
肥胖会引发慢性低度炎症，增加患结肠癌的风险。我们研究了巴多昔芬甲酯（BARD）对高脂饮食（HFD）诱导的小鼠结肠炎症的预防作用。将雄性C57BL/6J小鼠（n = 7）分为三组，分别给予高脂饮食（HFD组）、高脂饮食加饮用水中的BARD（10 mg/kg）（HFD/BARD组）或正常实验室普通饮食（LFD组），持续21周。在高脂饮食小鼠中，BARD降低了结肠厚度并减少了单位长度的结肠重量。这与结肠隐窝深度增加和每个隐窝杯状细胞数量增多有关。BARD降低了F4/80和CD11c的表达，但增加了CD206和IL-10的表达，表明具有抗炎作用。BARD阻止了细胞内促炎生物标志物（NF-қB、p NF-қB、IL-6、TNF-α）和细胞增殖标志物（Cox2和Ki67）的增加。BARD阻止了结肠壁中的脂肪沉积并防止了微生物群落变化。总体而言，我们报告了BARD通过调节巨噬细胞、NF-қB、细胞因子、Cox2和Ki67、脂肪沉积和微生物群对高脂饮食喂养小鼠的结肠炎症具有预防作用。
