西格列汀对肥胖合并脂肪肝大鼠的干预疗效

Effect of sitagliptin on the obese complicated with fatty liver rats

目的研究西格列汀对肥胖合并脂肪肝大鼠糖脂代谢及氧化应激的影响。方法高脂饮食成功构建肥胖合并脂肪肝模型。实验动物分为正常对照组(ND组)、肥胖对照组(OB组)、西格列汀干预组(ST组),每组8只。测定各组大鼠干预6周前后空腹血糖(FPG)、血清三酰甘油(TG)、空腹血清胰岛素(FINS)、血清超氧化物歧化酶(SOD)、血清谷胱甘肽过氧化物酶(GSH-Px)、血清丙二醛(MDA)的水平及干预后10%肝脏组织匀浆SOD、GSH-Px、MDA、TG水平,并计算胰岛素抵抗指数(HOMA-IR);油红O染色观察肝脏组织脂肪样变。结果 ST组与ND组比较,FPG、TG、FINS、HOMA-IR、血清MDA、血清及肝脏组织中SOD、GSH-Px浓度差异无统计学意义,ST组肝脏组织TG及MDA浓度升高(P<0.05),肝脏脂肪变性的程度增高;与OB组比较,ST组FPG、FINS、HOMA-IR、血清及肝脏组织TG、MDA浓度降低,血清及肝脏组织中SOD、GSH-Px浓度增高(P<0.05),肝脏脂肪变性的程度减低。结论西格列汀可通过改善氧化应激来改善肥胖合并脂肪肝大鼠的糖脂代谢,可能为治疗非酒精性脂肪肝提供新的药物选择。

Objective To evaluate the effects of treatment with sitagliptin on the oxidative stress and metaboism of glucose and fat in diet-induced obese and fatty liver rats. Methods Obese and fatty liver rats models were established by high fat food. All these rats were randomly divided into three groups： the normal group（ ND）,the obesity group（ OB）,the sitagliptin group（ ST）. There were 8 rats in every group. Body weight（ BW）,fasting blood glucose（ FPG）,triglyceride（ TG）,fasting insulin（ FINS）,serum SOD,GSH-Px,MDA were measured respectively before and after the 6 weeks of treatment and SOD,GSH-Px,MDA,TG in 10% liver homogenates were measured after sacrifice of the rats,and HOMA-IR was calculated. Oil red O staining was used to observe pathological changes in livers. Results The diameters： FPG,TG,FINS,HOMA-IR,serum MDA,the SOD and GSH-Px in both serum and liver homogenates of ND group and ST group were of no statistical significance,and the levels of TG and MDA in the liver homogenates of ST group were higher than ND group（ P〈0. 05）. The rats liver fatty degeneration in the ST group were more severe than those in the ND group. Compared with the OB group,the levels of FPG,TG,FINS,HOMA-IR and serum levels of MDA and TG in ST group decreased while the levels of SOD and GSH-Px in the serum and liver increased with a statistical significance（ P〈0. 05）. Meanwhile,the rats liver fatty degeneration in the ST group was less severe than those in the OB group. Conclusion Sitagliptin intervention can improve glucose and lipid metabolism,meantime,weaken oxidative stress and lower liver steatosis,suggesting that sitagliptin may act as potential therapeutic agent for non-alcoholic fatty liver.