成纤维细胞生长因子21对胰岛素抵抗缓解作用机制的研究  

Mechanisms of the role of fibroblast growth factor 21 in attenuating insulin resistance

作　　者：徐彤宇[1] 王文飞[1] 徐鹏飞[1] 袁清艳 刘双庆[1] 张童[1] 任桂萍[1] 李德山[1] 

机构地区：[1]东北农业大学生命科学学院,黑龙江哈尔滨150030

出　　处：《药学学报》2015年第9期1101-1106,共6页Acta Pharmaceutica Sinica

基　　金：黑龙江省发改委项目(黑发改项目[2011]1570号);黑龙江省教育厅科学技术研究项目(12521z004);黑龙江省高校科技成果产业化前期研发培育项目(1252CGZH29);黑龙江省博士后科研启动基金(LBH-Q09162);国家自然科学基金东北农业大学生物学理科基地科研训练及科研能力提高项目(J1210069/J0116);黑龙江省应用技术研究与开发计划项目(GC13C104)

摘　　要：本文考察了成纤维细胞生长因子21(FGF21)对胰岛素抵抗小鼠模型的治疗作用及其机制。采用高热量脂肪饮食联合小剂量链脲佐菌素建立2型糖尿病小鼠模型,随机分成2型糖尿病组与FGF21治疗高、低剂量组及胰岛素治疗组,并与正常对照组比较。测定5组间小鼠血清葡萄糖、胰岛素、脂质产物及血清和肝脏组织炎症因子水平的变化。结果显示,2型糖尿病组血糖、胰岛素、游离脂肪酸(FFAs)、甘油三酯及炎症因子平均水平较正常对照组显著增高(P<0.01),与胰岛素组比较无显著性差异。FGF21治疗组血糖、胰岛素、血脂及炎症因子平均水平较2型糖尿病组及胰岛素组显著降低(P<0.01),与对照组无差异。口服葡萄糖耐量试验(OGTT)及胰岛素抵抗指数(HOMA-IR)结果显示,经FGF21治疗4周后胰岛素抵抗亦明显得到改善,且呈现剂量依赖性。因此本研究揭示了FGF21可以改善2型糖尿病小鼠的胰岛素抵抗水平,可能与其参与调控炎症因子水平有关。This study is to evaluate the therapeutic effect of fibroblast growth factor 21（FGF21） on type 2 diabetic mice model and to provide mechanistic insights into its therapeutic effect. Type 2 diabetic animal model was established with high calorie fat diet and low dose streptozotocin（STZ） injection. Mice were then randomized into 5 groups： model control, FGF21 0.25 and 0.05 μmol·kg-1·d-1 groups, insulin treatment group. Ten age-matched normal KM mouse administered with saline were used as normal controls. Serum glucose, insulin, lipid products and the change of serum and liver tissue inflammation factor levels between five groups of mouse were determined. The results showed that blood glucose, insulin, free fatty acids（FFAs）, triglycerides, and inflammatory factor average FGF-21 of type 2 diabetes model group and normal control group were significantly higher（P〈0.01）, while compared with insulin group, no difference was significant. Average blood glucose, insulin, blood lipid and inflammatory factor of FGF-21 treatment group compared with type 2 diabetes group was significantly lower（P〈0.01） and insulin group has no difference with the model control group. The results of OGTT and HOMA-IR showed that insulin resistance state was significantly relieved in a dose-dependent manner. Thus, this study demonstrates that FGF-21 significantly remits type 2 diabetic mice model＇s insulin resistance state and participates in the regulation of inflammatory factor levels and type 2 diabetes metabolic disorders.

关 键 词：成纤维细胞生长因子21 胰岛素抵抗 2型糖尿病 炎症因子 

分 类 号：R963[医药卫生—微生物与生化药学]