脂肪组织TLR-4/NF-κB信号通路与高脂饮食诱导小鼠胰岛素抵抗的关系

目的采用高脂饮食诱导小鼠胰岛素抵抗,了解脂肪组织Toll样受体4（Toll-like receptor 4,TLR-4）、神经因子κB（nuclear factorκappa B,NF-κB）信号通路与胰岛素抵抗的关系。方法 C57BL/6雄性小鼠80只,随机分为2组,分别给予普通饮食和高脂饮食喂养,每组随机抽样分为4亚组,各5只小鼠,分别于喂养12周后监测体质量、空腹血糖、血清胰岛素水平;处死后取脂肪组织,经苏木精-伊红（Hematoxylin-Eosin,HE）染色观察脂肪组织形态变化;Western blot法检测小鼠脂肪组织TLR-4、NF-κB蛋白表达。免疫组化法检测肿瘤坏死因子α（tumor necrosis factorαlpha,TNF-α）及白细胞介素6（interleukin 6,IL-6）表达。结果高脂喂养小鼠胰岛素抵抗模型建立成功;高脂组发生胰岛素抵抗,对照组未发生胰岛素抵抗;高脂组小鼠的体质量、空腹血糖、胰岛素水平较对照组明显升高（P〈0.05）,脂肪组织HE染色显示脂肪细胞逐渐增大;脂肪组织TLR-4/NF-κB蛋白从第3天开始出现高表达,到第5天开始达到高峰,并且一直持续在较高水平,同时脂肪细胞也出现TNF-α、IL-6的明显表达。结论高脂饮食可激活脂肪细胞TLR-4/NF-κB信号通路,并与胰岛素抵抗之间具有关联性。

Relationship between Adipose Tissue TLR-4/NF-κB Signaling Pathway and High-fat Diet Induced Insulin Resistance in Mice

Objective To explore the relationship between the Toll-like receptor 4 （TLR-4） / nuclear factor Kappa B （NF-κB） signaling pathway and high-fat diet induced insulin resistance in mice adipose tissues. Methods Eighty C57BL/6 mice were randomly divided into two groups fed with normal diet and high fat diet respectively, and then randomly divided into eight subgroups in 12 weeks.The weight, fasting blood glucose and serum insulin levels were detected, and the adipose tissue was observed through tissue slice with Hematoxylin-Eosin （HE） staining. Immunohistochemistry was used to detect the expression of inflammation factors such as tumor necrosis factor alpha （TNF-α） and interleukin 6 （IL-6） so as to describe the formation and development of fat local inflammation. Finally, the Western blot method was a- dopted to detect proteins of TLR-4/NF-κB. Results High-fat feeding induced insulin resistance model successfully. IR was verified in model group, but not in normal conrol （NC） group. The levels of the weight and the blood glucose in mod el group were markedly increased compared with NC group （P〈0.05） and high-fat diet induced the expression of TLR-4 mRNA and protein in adipose tissue. TLR-4/NF ~B signaling pathway activation increased gradually along with the days of high-fat diet, and reached a maximum level at the fifth clay. The adipose tissue increased TNF-α and IL6 expression in parallel, and the fat cells became bigger.Conclusion The high expression of TLR-4/NF-κB in adipose tissue and the in creasing of serum insulin is consistent. The high-fat diet can activated fat cells TLR-4/NF-κB signaling pathways, and have the association with the insulin resistance.