【作者】 罗莉；

【导师】 王长江；

【作者基本信息】 安徽医科大学 ， 内分泌与代谢病， 2010， 硕士

【摘要】 背景代谢综合征发生、发展的中心环节是体内存在胰岛素抵抗,而中心性肥胖是导致胰岛素抵抗的主要原因。Visfatin(内脏脂肪素)是脂肪组织所产生的分泌性蛋白,主要由内脏脂肪组织分泌产生,在肝脏、胰腺、心脏、胎盘、肺、肾等许多组织也有表达。研究表明,Visfatin有类胰岛素样作用,对改善胰岛素敏感性非常重要。二甲双胍,有氧运动可以减轻体重,改善胰岛素敏感性,但目前国内外鲜有Visfatin与二者关系的报道。本研究通过高脂饮食诱导肥胖大鼠,观察二甲双胍、有氧运动干预后Visfatin的变化,并初步探讨其可能的机制。目的观察二甲双胍,有氧运动分别及联合干预对高脂饲料诱导的肥胖大鼠血清、附睾脂肪、皮下脂肪、肝脏组织Visfatin及相关代谢指标的影响。方法将70只雄性6周龄Sprague-Dawley(SD)大鼠随机分为普通饮食组(ND, n=10),给予普通饲料喂养;高脂饮食组(HD, n=60),给予高脂饲料喂养。16周后,高脂饮食组大鼠体重均数高于普通饮食组大鼠20%,成功建立模型。所有大鼠过夜禁食后,麻醉状态下测量体重(BW),取静脉血测定血清甘油三酯(TG)、总胆固醇(TCH)、空腹血糖(FBG)、空腹胰岛素(FINS)及Visfatin。将40只达到肥胖模型标准的大鼠随机分为4组,每组各10只,在继续高脂饮食的同时给予不同干预。分别为:肥胖对照组(F组),二甲双胍干预组(M组),有氧运动干预组(T组),二甲双胍、有氧运动联合干预组(MT组)。M组予二甲双胍灌胃(200mg/kg.d),T组进行游泳运动,MT组予二甲双胍灌胃(200mg/kg.d)联合游泳运动,T组、F组及ND组等剂量蒸馏水灌胃。第22周再次测量体重(BW),取静脉血测定血清甘油三酯(TG)、总胆固醇(TCH)、空腹血糖(FBG)、空腹胰岛素(FINS)及Visfatin。处死大鼠后,采用免疫印迹法(Western blot方法)测定各组大鼠附睾脂肪,皮下脂肪,肝脏组织Visfatin蛋白的表达。结果①高脂饲料喂养16周后,与ND组相比较,F组大鼠的体重、空腹血糖、空腹胰岛素、血清甘油三酯(TG)、总胆固醇(TCH)均升高(P <0.01或0.05)。②F组大鼠血清Visfatin较ND组升高(P < 0.01)。③与F组比较,M组、T组、MT组大鼠体重、空腹血糖、空腹胰岛素、血清甘油三酯(TG)、总胆固醇(TCH)均下降(P <0.01或0.05)。④M组、T组、MT组大鼠血清Visfatin较F组下降(P <0.01或0.05)。⑤M组、T组、MT组大鼠之间以上指标无明显差异。⑥F组附睾脂肪,皮下脂肪,肝脏组织Visfatin的蛋白表达较ND组增加(P <0.05)。⑦M组、T组、MT组附睾脂肪,皮下脂肪,肝脏组织Visfatin的蛋白表达较F组减少(P <0.05)。⑧BW、TG、TCH、FBG、FINS水平与血清Visfatin水平呈正相关(r=0.86, P<0.01; r=0.83, P<0.01; r=0.88, P<0.05; r=0.91, P<0.05; r=0.85, P<0.05 )结论二甲双胍、有氧运动分别及联合应用可以一定程度改善高脂诱导肥胖大鼠代谢综合征状态,降低血清Visfatin浓度,并能下调附睾脂肪、皮下脂肪及肝脏Visfatin的蛋白表达。更多还原

【Abstract】 Background The central link of metabolism syndrome is insulin resistence,the main reason of which is central obesity. Visfatin is a kind of secretory protein generated by adipose tissue,Which is mainly secreted by adipose tissue of internal organs, and also expressed in liver, pancreas, heart, placenta, lung, kidney etc. Researches show that Visfatin can play an insulin-like effect which is important to improve insulin sensitivity. As is known to all, both metformin and aerobic exercise can reduce weight and improve insulin sensitivity,but the relation between Visfatin and those two factors has been rarely reported.In this study,we try to observe the effects of aerobic exercise and metformin on Visfatin in obesity rats fed with high fat diet and to preliminarily investigate the mechanism.Objective To observe the effects of metformin and aerobic exercise on Visfatin of serum,epididymis adipose tissue ,subcutaneous adipose tissue and liver in obesity rats fed with high fat diet.Methods 70 male Sprague-Dawley(SD) rats were randomly divided into the normal diet group (ND) with 10 rats, fed with normal chow , the high fat diet group (HD) with the remaining 60, fed with high fat diet.After 16 weeks, the average BW of HD group were over 20% higher than ND group. All the rats were weighed under anesthesia. The triglyeride(TG), total cholesterol(TCH), fasting blood glucose(FBG), fasting insulin(FINS) and Visfatin in the serum were measured. Obesity model (n=40) was randomly divided into four groups accepting intervention for 6 weeks: group F,group M, group T and group MT,with 10 rats in each groups. Group M was treated with metformin (200mg/kg.d), group T was assigned to swimming exercise, and group MT was treated with the combination of metformin(200mg/kg.d) and swimming exercise. Group T, group F and group ND were treated with distilled water . The body weight (BW), triglyeride(TG), total cholesterol(TCH), fasting blood glucose(FBG), fasting insulin(FINS) and Visfatin in the serum were measured again at the end of 22nd week.After all the rats were killed, the protein levels of Visfatin in different tissues(epididymis adipose tissue ,subcutaneous adipose tissue and liver) were analyzed with Western blot.Results①After 16 weeks of high-fat diet, BW, FBG, FINS ,TG and TCH levels of each group in obesity model were higher than that in ND group with a statistical significance (P <0.01 or P <0.05).②Visfatin in the serum in obesity model were higher than that in ND group(P < 0.01).③After 6 weeks’treatment BW, FBG, FINS ,TG and TCH levels in the group M, T and MT decreased compared to group F (P <0.01 or P <0.05).④Visfatin in the serum in the group M, T and MT decreased compared to group F(P <0.01 or P <0.05).⑤There is no statistical difference of BW, FBG, FINS ,TG, TCH and Visfatin levels in the group M, T and MT.⑥Visfatin protein expression levels of group F in EAT, SAT and LT increased compared to group ND(P <0.05).⑦Visfatin protein expression levels of group M, T and MT decreased in compared to group F in EAT, SAT and LT(P <0.05).⑧BW,TG、TCH、FBG、FINS were positively related to serum Visfatin levels(r=0.86, P <0.01; r=0.83, P <0.01; r=0.88, P <0.05; r=0.91, P <0.05; r=0.85, P <0.05 ).Conclusion Metformin,aerobic exercise , the combination of metformin and aerobic exercise can improve the metabolism syndrome of rats fed with high fat diet to certain extent, and decrease the concentration of Visfatin of serum, epididymis fat, subcutaneous fat and liver in obesity rats.更多还原