沙格列汀对糖尿病合并非酒精性脂肪性肝病大鼠模型肝脏炎症损伤的保护作用及机制  

Protection of Saxagliptin for liver inflammatory injury in rat model of diabetes complicating with nonalcoholic fatty liver disease and its mechanism

作　　者：罗惠金 刘艳[1] 陈容平[1] 张双双[1] 陈宏[1] 张振[1] 

机构地区：[1]南方医科大学珠江医院内分泌科,广州510282

出　　处：《中华内分泌代谢杂志》2015年第6期538-540,共3页Chinese Journal of Endocrinology and Metabolism

基　　金：广东省医学科学技术研究基金

摘　　要：将32只雄性 SD 大鼠随机分为正常对照组（NC,n=10）和高脂组（HF,n=22）。 NC 组大鼠予标准饲料喂养,HF 组大鼠予高糖高脂饲料喂养10周末腹腔注射小剂量 STZ（30 mg/ kg）进行糖尿病造模,并将造模成功的非酒精性脂肪性肝病（NAFLD）合并糖尿病大鼠随机分为模型对照组（MC,n =8）及沙格列汀干预组（M＋S,n=8）,其中 M＋S 组给予沙格列汀（10 mg·kg-1·d-1）灌胃8周,其余两个对照组给予同体积生理盐水灌胃。检测血糖、胰岛素、肝功能、肝湿重、肿瘤坏死因子α及白细胞介素6,计算胰岛素抵抗指数（HOMA-IR）；检测 NF-κB 在肝组织的表达。结果提示 MC 组上述检测指标水平均高于 NC 组,M＋S 组上述指标较 MC 组均有显著改善。与 NC 组相比,MC 组 NF-κB 表达增多,与 MC 组相比,M＋S 组 NF-κB 表达减少。相关分析显示,TNF-α及 IL-6分别与 HOMA-IR 呈正相关。提示沙格列汀可有效降低血糖水平、在一定程度上减轻胰岛素抵抗,并进一步减轻肝脏的炎症损伤,对受损肝细胞起到一定的保护作用。[Summary] Thirty-two SD rats were randomly divided into noraml control group（NC, n = 10） and high fat diet group（HF, n=22）. 10 weeks later, the HF group rats were injected STZ（30 mg/ kg） to set up the model of diabetes complicating with nonalcoholic fatty liver disease （NAFLD）. Then, HF group were randomly divided into model control group（MC, n = 8） and Saxagliptin intervene group（ M ＋ S, n = 8）. The M ＋ S group were made an intervention with Saxagliptin（10 mg·kg-1 ·d-1 ） for 8 weeks. At the end of 18 weeks, the fasting blood glucose, serum insulin, liver function, liver weight, tumor necrosis factor alpha, and interleukin 6 were measured. HOMA-IR was calculated. Western bolt was used to determine the expression of NF-κB in hepatic tissue. The level of the indexes above increased in the MC group than in the NC group. But the indexes above mentioned in M ＋ S group were ameliorated. The expression of NF-κB was significantly up regulated in MC group as compared with the NC group, and significantly reduced in the M＋S group than in the MC group. The results of correlation analysis revealed that TNF-αand IL-6 were positive correlated with HOMR-IR, respectively. Saxagliptin can effectively reduce the blood glucose level and alleviate insulin resistance, then further relieve the inflammation of liver injury, and finally to alleviate the condition of T2DM with NAFLD. It may play a protective role in the damaged hepatic cells.

关 键 词：沙格列汀 非酒精性脂肪肝 糖尿病  实验性 炎症 

分 类 号：R575.5[医药卫生—消化系统]