西格列汀对2型糖尿病大鼠chemerin水平的影响

The influence of sitaglipin on chemerin levels of type 2 diabetic rats

目的研究西格列汀干预对2型糖尿病(T2DM)大鼠各代谢指标及脂肪因子chemerin水平的影响及其可能的机制,并探讨脂肪因子chemerin与T2DM的关系。方法将35只雄性SD大鼠随机分为普通饲料喂养组(NC组,n=10)及高脂饲料喂养组(HF组,n=25),12周后将高脂饮食喂养的大鼠腹腔一次性注射链脲佐菌素(STZ)35 mg/kg,T2DM大鼠造模成功(n=20)后随机分为两组:T2DM对照组(T2DM组,n=10)、西格列汀干预组(SP组,n=10),ELISA法分别测定干预前后各组大鼠生化指标,Western blot法检测大鼠肾周脂肪、肝脏和肌肉组织chemerin蛋白表达水平。结果 1 T2DM大鼠的血清chemerin、体重(BW)、空腹血糖(FBG)、胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、胰岛素抵抗指数(HOMO-IR)与NC组比较均增高,胰岛β细胞功能指数(HOMO-β)降低,肾周脂肪、肝脏及肌肉组织的chemerin蛋白表达量增加;2西格列汀可降低T2DM大鼠FBG、FINS、TC、TG、LDL、HOMO-IR、血清chemerin水平及肾周脂肪、肝脏组织的chemerin蛋白表达量,提高HOMO-β指数;3相关性分析显示西格列汀干预前后TG、FINS及HOMO-IR始终与chemerin独立相关。血清chemerin水平与肾周脂肪chemerin蛋白表达量呈正相关(r=0.79,P<0.05)。结论西格列汀可降低血清、肾周脂肪及肝脏组织中chemerin水平,改善血清学各代谢指标,chemerin可能参与T2DM的发生发展。

Objective To investigate the effects of sitagliptin on metabolic parameters and chemerin levels of type 2 diabetic rats, and to explore the relationship between chemerin and type 2 diabetes. Methods A total of 35 male SD rats were randomly divided into normal diet group （NC, n=10） and a high-fat diet group （HF, n=25）. Af-ter 12 weeks, high-fat diet rats were given an injection of 35 mg/kg streptozotocin at a time,then the diabetic model rats （n=20） were randomly divided into 2 groups：diabetes control group （T2DM, n=10） and sitagliptin inter-vention group （SP, n=10）. The rats＆#39;metabolic parameters were measured by ELISA. The chemerin protein expres-sion levels in kidney adipose, liver and muscle tissue were detected by Western blot. Results ① The serum chemerin,FBG, FINS, TCH, TG, LDL, HOMO-IR levels of diabetic model group were increased. HOMO-beta decreased. Chemerin expression levels of diabetes control group in adipose, liver and muscle tissue increased com-pared with NC group;② Sitagliptin could down-regulate the levels of BW, FBG, FINS, TC, TG, LDL, HOMO-IR,serum chemerin and chemerin levels in adipose and liver tissues. On the contrary,HOMO-beta was up-regula-ted;③ The correlation analysis showed that TG, FINS and HOMO-IR were always independently associated with chemerin. In tissues, serum chemerin had positive correlation with chemerin expression levels in adipose. Conclu-sion Sitagliptin can reduce the levels of chemerin in serum and tissues. It also can improve the metabolic indexes remarkably in serum. Chemerin may be a key involving element in the development of diabetes.