沙格列汀对高糖高脂饮食大鼠糖脂代谢的影响及其对脂肪因子的作用  

Efficacy of Saxagliptin on glucose and lipids metabolism and adipokines in high-glucose and fat dietinduced insulin resistance rats

作　　者：张奇志[1] 陈诗鸿[1] 王蒙[1] 庄向华[2] 

机构地区：[1]山东省交通医院心内科,济南250031 [2]山东大学第二医院内分泌科

出　　处：《中华老年医学杂志》2014年第3期315-318,共4页Chinese Journal of Geriatrics

基　　金：国家自然科学基金项目（81070641）;山东省自然科学基金项目（2009ZRB0149K4）;山东省科技发展计划（2010GSF10231）

摘　　要：目的观察沙格列汀对高糖高脂饮食诱导的肥胖大鼠糖脂代谢的影响，探讨沙格列汀改善糖尿病的可能作用机制。方法将4周龄雄性Wistar大鼠36只随机分为2组，对照组12只，高糖高脂饮食组24只。8周后高糖高脂组再随机分为高脂组和沙格列汀干预组，继续喂养8周。测定大鼠血糖、胰岛素、血脂、肿瘤坏死因子α（TNF-α、脂联素水平。结果（1）高脂组与对照组比较，空腹血糖[（7．07士1．61）mmol/L比（5．10-4-0．44）mmol/L]、胰岛素[（23．70±7．37）mU/L比（19．35士6．38）mU/L）]、血清三酰甘油[（3．21士1．44）mmol/L比（0．83±0．39）mmol/L]、胆固醇[（3．04±1．62）mmol/L比（1．14土0．24）mmol/L]水平均升高，沙格列汀干预后上述指标下降；葡萄糖输注率高脂组低于对照组[（18．80±1．57）mg·kg^-1·min^-1比（24．31±2．65）mg·kg^-1·min^-1）]（P〈0．01），且低于干预组[（21．45士1．80）mg·kg^-1·min^-1]（P〈0．05）。与对照组比较，高脂组大鼠血清TNF-α[（1．38±0．18）ug/L比（2．33±0．21）p．g/L]浓度显著升高，脂联素[（2．65士0．29）mg/L比（1_38士0．20）mg/L]水平显著降低（P〈0．01）；干预组与高脂组比较，血清TNF-α浓度降低（P〈0．01），脂联素水平升高（P〈0．05）。结论高糖高脂饮食导致大鼠胰岛素抵抗，应用沙格列汀干预后大鼠胰岛素抵抗改善，血脂水平降低，脂肪因子水平发生显著改变。Objective To investigate the efficacy of Saxagliptin on the glucose and lipids metabolism and adipokines levels in diet-induced insulin resistance rat, and to explore the regulatory mechanism of saxagliptin in insulin resistance. Methods 36 4-week-old male Wistar rats were randomly divided into two groups., control group （n= 12） and high-glucose and fat diet group（HF, n =24）. The HF rats were randomly divided into two subgroups： HF group and saxagliptin group, and continued the treatment for 8 weeks. Levels of blood glucose, insulin, triglyceride （TG）, total cholesterol （TC）, TNF-a and adiponectin were determined. Results After four months, serum levels of fasting glucose, insulin, TG, TC were significantly increased in HF group as compared with control group [（7.07±1.61） mmol/L vs. （5. 104±0.44） mmol/L, （23. 704±7.37） mU/L w （19.35 ±6.38） mU/L], [（3.21±1.44） mmol/L w （0.83±0.39） retool/L, （3.04± 1.62） mmol/L w （1.14±0.24） mmol/L, all P〈0. 051, and were all decreased after the treatment of saxagliptin. The glucose infusion rate was lower in HF group than in control group and was higher in saxagliptin group than inHFgroup [（18. 804±1.57） mg.kg^- 1 . min^-1 vs （24.31±2.65） mg . kg-1 . min^-1, （21.45 ±1.80） mg, kg^-1 . min^-1vs （18.80±1.57） mg . kg^-1 . min^-1 P〈0.01 or 0.051. Compared with the control group, serum THF-α was higher and adiponectin level was lower in HF group [（1.38±0.18） μg/L vg （2.33±0.21）μg/L, （2.65±0.29） mg/L vs （1.38=t=0. 20）rag/L, both P〈0. 011 ]Saxagliptin can significantly increase the serum level of adiponectin and decrease the level of TNF-αin HF group （ P〈O. 01 or O. 05）. Conclusions Saxagliptin treatment can improve high-fat diet- induced insulin resistance, decrease blood lipids levels and regulate the levels of adipokines in HF rats.

关 键 词：胰岛素抗药性 脂肪因子类 

分 类 号：R965[医药卫生—药理学]