[关键词]
[摘要]
探讨槲皮素干预对高脂饮食诱导肥胖小鼠结肠组织炎症的改善作用及机制。将30只雄性C57BL/6J小鼠随机分为3组:低脂对照组(low-fat diet, LF)、高脂喂养组(high-fat diet,HF)、高脂喂养+槲皮素干预组(50 mg/kg·BW,HF+Q)。槲皮素干预的给药方式为灌胃给予,每天灌胃1次,持续20周。采用苏木精-伊红染色观察结肠组织形态结构,ELISA试剂盒检测肠内容物中脂多糖(LPS)含量,Real-time PCR和Western Blotting测定结肠中细胞因子[白介素-1β(IL-1β)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)]水平,以及检测槲皮素干预对TLR4/NF-κβ信号通路的影响。槲皮素干预显著减少肥胖小鼠的体重增加(p<0.05),修复结肠组织形态学上的损伤,能够显著降低LPS含量至5.04 ng/mL(vs HF组:7.01 ng/mL,p<0.05),分别抑制结肠组织中炎性因子TNF-α(39.04%)、IL-1β(17.73%)和IL-6(25.47%)的蛋白表达,以及抑制TLR4/NF-κβ信号通路的激活。结论提示,槲皮素对肥胖小鼠结肠组织炎症具有改善作用,减少炎性因子的表达,其作用机制可能和抑制TLR4/NF-κβ信号通路的激活相关。
[Key word]
[Abstract]
The effects of quercetin on colonic inflammation in a mouse model of high-fat diet-induced obesity were investigated in this study. Thirty male C57BL/6J mice were randomly divided into three groups, including low-fat diet group (LF), high-fat diet group (HF), and high-fat diet feeding with quercetin group (50 mg/kg·BW, HF+Q). Quercetin was administered orally once a day for 20 weeks. The morphology of colon was observed by hematoxylin-eosin staining. The concentration of LPS was detected by ELISA. The levels of cytokines, including IL-6、IL-1β and TNF-α were measured by Real-time PCR and western blotting. The activation of the TLR4/NF-kβ signaling pathway was determined by western blotting. The HFD-induced body weight gain was significantly reduced by quercetin in obese mice (p<0.05). Besides, the colonic morphological damage was ameliorated, and the concentration of LPS was reduced to 5.04 ng/mL (compared with HF group: 7.01 ng/mL, p<0.05) by quercetin. Compared with the HF group, the protein expressions of TNF-α (39.04%), IL-1β (17.73%) and IL-6 (25.47%) were inhibited by quercetin, and the activation of TLR4/NF-kβ signaling pathway was inhibited by quercetin. In conclusion, tissue inflammation in colon of obese mice can be improved and the expression of inflammatory factors can be reduced by quercetin. The mechanism may be associated with the reducing the activation of TLR4/NF-kβ signaling pathway.
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[基金项目]
国家自然科学基金青年项目(81703219);广州医科大学大学生实验室开放项目(2018);广州市科技计划项目(201904010404)