胰腺组织TLR4及其炎症因子在高脂饮食诱导小鼠胰岛素抵抗中的表达  

Pancreatic tissue TLR4 and inflammatory factor expression in high-fat diet insulin resistance in mice

作　　者：王晓静[1] 魏琴[2] 吴鸿涛[1] 杨凯[1] 娜仁花[1] 王宁[1] 

机构地区：[1]新疆医科大学第一附属医院干部病房内一科,乌鲁木齐830054 [2]新疆医科大学第一附属医院临床研究中心,乌鲁木齐830054

出　　处：《新疆医科大学学报》2014年第5期557-560,564,共5页Journal of Xinjiang Medical University

基　　金：国家自然科学基金(30801019)

摘　　要：目的观察高脂饮食模型小鼠胰腺组织Toll样受体4(Toll like receptor,TLR4)、核因子-kappa B(Nucler factor-κB)表达的变化,了解小鼠胰腺组织TLR4/NF-κB信号通路的变化,及其与胰岛素抵抗的关系。方法C57BL/6雄性小鼠80只,随机分为两组,分别给予普通饮食和高脂饮食喂养,每组又随机抽样分为8个亚组,每组各5只小鼠,分别于喂养12w后监测体质量、空腹血糖、血清胰岛素水平;处死后取胰腺组织,苏木精-伊红染色(Hematoxylin-Eosin staining,HE),观察胰岛细胞形态变化;Western blot法检测小鼠胰腺组织TLR4、NF-κB蛋白的表达。免疫组织化学法检测肿瘤坏死因子(TNF-α)及白介素6(IL-6)表达水平。结果高脂饮食成功诱导小鼠胰岛素抵抗模型,胰岛细胞大体体积显示先增大后缩小。胰腺组织TLR4/NF-κB蛋白从第7天出现高表达,第21天达高峰,随后逐渐下降,同时胰岛细胞中也出现TNF-α、IL-6的表达。结论高脂饮食可激活胰腺组织TLR4/NF-κB信号通路,并与胰岛素抵抗具有相关性。Objective The study aims to explore the relationships between the TLR4/NF-κB signaling path-way and high-fat-diet-induced insulin resistance in mice pancreatic tissue.Methods C57BL/6 mice（80） were randomly divided into two groups,which were fed with normal diet and high fat diet respectively, and then randomly divided into eight groups according to the feeding days （0,3,7,11,14,21,42,84days re-spectively）.The weight,fasting blood glucose and serum insulin levels were detected,and the pancreatic tissue was observed through tissue slice with HE.Immunohistochemistry was used to detect the expression of inflammation factors such as TNF-α,IL-6 so as to describe the formation and development of fat local inflammation.Finally,the Western-blot method was adopted to detect proteins of TLR4/NF-κB.Results The results showed that the mice insulin resistance model was successfully created with high-fat diet,and high-fat diet induced the expression of TLR4 mRNA and protein in pancreatic tissue.TLR4/NF-κB signa-ling pathway activation increased gradually with the seven days of high-fat diet given,which reached a maximum level on the 2 1 st day.The islet cell increased TNF-αand IL-6 expression.Conclusion The high-fat diet can activate fat cells TLR4/NF-κB signalingpathways,and it had the association with the insulin resistance.

关 键 词：TOLL样受体4 核因子-KAPPA B TLR4 炎症因子 胰腺组织 胰岛素抵抗 

分 类 号：R365[医药卫生—病理学]