摘要
目的观察过氧化物酶体增殖剂激活受体γ(peroxisome proliferator-activated receptorγ,PPARγ)激动剂吡咯列酮对高脂饮食诱导肥胖大鼠胰岛素抵抗和肝脏脂肪代谢的影响。方法雄性Wistar大鼠随机分为空白对照组、吡咯列酮组、高脂饮食组、高脂饮食+吡咯列酮组,每组12只。空白对照组和吡咯列酮组给予普通维持饲料饲养,高脂组和高脂饮食+吡咯列酮组给予高脂饲料(high fat diet,HFD)饲喂,分别于实验第8周尾静脉取血进行葡萄糖耐量试验(glucose tolerance test,GTT),第9周进行胰岛素耐量试验(insulin tolerance test,ITT),动物恢复1周,自11~12周,吡咯列酮组和高脂饮食+吡咯列酮组动物分别经口给予10 mg/kg·bw吡咯列酮,然后经尾静脉取血,再次检测动物GTT和ITT。待动物恢复后,腹主动脉取血后处死动物,迅速分离肝脏,制备肝脏冰冻切片进行肝脏油红O染色检测脂肪蓄积情况,采用生化法分别检测肝脏甘油三酯(triglyceride,TG)和游离脂肪酸(free fatty acid,FFA)含量,Western blot测定各组动物肝脏PPARγ及其下游蛋白脂联素(adiponectin)表达水平。结果实验期间,各种动物体重均呈增长趋势,HFD组动物在第4周时体重明显高于普通饲料喂饲动物(P<0.05),常规饲料和HFD喂饲导致的体重差异保持至实验结束(P<0.05);肝脏油红O染色结果显示HFD导致动物肝脏脂肪蓄积;GTT和ITT提示HFD组动物出现明显的葡萄糖代谢受损和胰岛素抵抗(P<0.05)。给予吡咯列酮干预2周,与普通饲料组动物相比,HFD组动物体重未观察到明显降低,但GTT和ITT显示吡咯列酮能够明显缓解HFD诱导的动物胰岛素抵抗(P<0.05),肝脏脂肪蓄积明显减轻,PPARγ和脂联素蛋白表达水平高于高脂饮食组(P<0.05)。结论吡咯列酮能够明显减轻高脂饮食引起的大鼠胰岛素抵抗和肝脏脂肪蓄积,激活PPARγ促进肝脏脂肪分解可能是其机制之一。
Objective To observe the effects of pioglitazone on insulin resistance and hepatic fat metabolism in obese rats induced by high fat diet. Methods Adult male Wistar rats were randomly divided into control(Con)group,pioglitazone(Pio)group,high fat diet(HFD) group,high fat diet + pioglitazone(HFD+Pio)group,with 12 rats in each group respectively.The control group and the pioglitazone group were fed with chow diet.The high-fat group and the HFD + pioglitazone group were fed with high-fat diet.Glucose tolerance test(GTT)and insulin tolerance test(ITT)were performed to determine the glucose metabolism disorder in rats by blood sampling from the tail vein at 8 th and 9 th weeks respectively.From 11 th week to 12 th week,the rats in the pioglitazone group and the HFD + pioglitazone group were orally given pioglitazone at a dose of 10 mg/kg·bw,and followed by the GTT and ITT respectively.Then,the rats were sacrificed and livers were dissected quickly.Liver triglyceride(TG) and free fatty acid(FFA)were measured by commercial test kits and the fat accumulation were revealed by the oil red O staining.The liver adiponectin and peroxisome proliferator-activated receptor γ(PPARγ)levels were determined by Western blot. Results The body weight of rats in each group kept a steady increasing during the experiment period.The body weight of rats fed with HFD were significantly higher than the chow diet-fed rats(P<0.05)since the 4 th week,and this difference between HFD and chow diet group was kept till the end of the experiment(P<0.05).GTT and ITT revealed that the HFD disturbed the glucose tolerance and insulin tolerance of rats(P<0.05),accompanied with the liver fat accumulation.Then,the rats were treated with pioglitazone for 2 weeks,the body weight of rat fed with HDF was not significantly decreased,but results of GTT and ITT revealed that pioglitazone significantly improved HFD-induced insulin resistance in rats(P<0.05)and reduced liver fat accumulation.In addition,the expression of PPARγ and adiponectin in liver of rats wer
作者
田奥
邵根
冯赫平
邱晓菲
张一帆
赵秀兰
TIAN Ao;SHAO Gen;FENG He-ping;QIU Xiao-fei;ZHANG Yi-fan;ZHAO Xiu-lan(School of Public Health,Shandong University,Jinan,Shandong,250012,China)
出处
《预防医学论坛》
2020年第2期81-84,88,共5页
Preventive Medicine Tribune
基金
山东省自然科学基金(ZR2017MH002)
山东省重点研究计划(医用食品专项计划,2017YYSP022)
大学生创新计划(2018035)。
