【摘要】 目的观察食源性肥胖大鼠下丘脑结节性硬化症基因1(tuberous sclerosis complex 1,Tsc1)启动子区甲基化率及哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)的表达。方法 16只雄性SD大鼠分为高脂喂养组和基础饲料喂养组(对照组),每组8只,共喂养12周。测定两组大鼠体质量、腹腔脂肪量、腹腔脂肪/体质量比值,采用重亚硫酸盐的测序法检测Tsc1启动子甲基化,RT-PCR、Western blot分别检测mTOR mRNA和蛋白表达。结果高脂组大鼠体质量、腹腔脂肪量、腹腔脂肪/体质量比均高于对照组(P<0.05)。两组大鼠下丘脑Tsc1启动子区均有11个位点可被甲基化,食源性肥胖组甲基化率(94.50%±4.66%)高于对照组(86.60%±3.49%,P<0.002),mTOR mRNA和蛋白表达均高于对照组(P<0.05)。结论食源性肥胖大鼠下丘脑Tsc1基因启动子甲基化率增加,其下游基因mTOR表达上调,可能参与了肥胖的发生。更多还原

【Abstract】 Objective To investigate the methylation rate of tuberous sclerosis complex 1(Tsc1)promoter and expression of mammalian target of rapamycin(mTOR)in food-induced rat hypothalamus.Methods 16 male SD rats were divided into high fat diet induced group(8rats)and normal control group(8rats)feeding for 12 weeks.Body mass,mass of celiac fat,celiac fat/body mass were measured.Methylation of Tsc1 promoter,mRNA and protein expression of mTOR were detected by bisulfite sequencing method, RT-PCR and Western blot,respectively.Results Mass of celiac fat,celiac fat/body mass were higher in food-induced rat than that in control group.There were 11 methylation sites in SD rat hypothalamus.Obese group has significantly higher methylation rates(94.50% ±4.66%)than that of control group(86.60% ±3.49%)(P<0.002).The mRNA and protein expression of mTOR were noted lower in control group than in obese group(P<0.05).Conclusion The increased methylation rate of Tsc1 promoter in food-induced rat hypothalamus and up-regulated expression of mTOR,downstream gene of Tsc1 may promote the obesity.更多还原