白藜芦醇对高脂饮食诱导小鼠高脂血症的作用机制研究

Effects and mechanism of resveratrol on hyperlipidemia induced by high-fat diet in mice

目的考察白藜芦醇对高脂血症小鼠的影响,并探讨其作用机制。方法按体重将雄性C57BL/6J小鼠随机分为3组:正常组、模型组及实验组,每组10只。正常组正常饲养,模型组及实验组小鼠连续饲喂4周高脂饲料构建高血脂模型。建模后,实验组灌服白藜芦醇(400 mg·kg^(-1)),模型组及空白组灌服等量生理盐水,每天1次,连续干预4周。全自动生化分析仪检测小鼠血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)水平;称量小鼠肝重量,计算各组小鼠肝指数;蛋白质印迹法检测肝组织丝氨酸/苏氨酸蛋白激酶(Akt)、磷酸化Akt(p-Akt)及哺乳动物雷帕霉素靶蛋白(mTOR)蛋白表达。结果正常组、模型组和实验组的血清TG水平分别为(0.70±0.19),(0.97±0.19)和(0.86±0.14)mmol·L^(-1);TC水平分别为(2.08±0.33),(3.59±0.32)和(3.03±0.32)mmol·L^(-1);LDL-C水平分别为(0.26±0.04),(0.50±0.08)和(0.41±0.04)mmol·L^(-1);HDL-C水平分别为(1.67±0.08),(2.47±0.24)和(2.67±0.30)mmol·L^(-1);小鼠肝指数分别为3.04±0.31,3.67±0.17和3.29±0.23;肝组织中Akt蛋白相对表达量分别为0.78±0.11,1.38±0.18和0.86±0.08;p-Akt蛋白相对表达量分别为0.43±0.08,0.88±0.14和0.62±0.25;mTOR蛋白相对表达量分别为0.80±0.05,1.85±0.23和1.16±0.17。上述指标:模型组与正常组相比,差异均有统计学意义(均P<0.05),实验组的TC、LDL-C、Akt和mTOR水平与模型组比较差异均有统计学意义(均P<0.05)。结论白藜芦醇能够明显改善高脂饮食诱导的小鼠高脂血症,其机制与抑制肝内Akt/mTOR通路的激活有关。

Objective To investigate the effect of the resveratrol on high fat diet induced hyperlipidemia in mice and to explore its mechanism of action.Methods Male C57BL/6J mice were randomly divided into three groups by body weight:normal group,model group and experimental group,with 10 mice in each group.The normal group was fed normally,and the mice in the model and experimental groups were fed with high-fat diet for 4 weeks to construct a hyperlipidemia model.Then the experimental groups were given 400 mg·kg^(-1) resveratrol by gavage after modeling,the normal group and the model group were given the same amount of normal saline,once a day for 4 weeks of continuous intervention.Mice serum triglyceride (TG),total cholesterol (TC),low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were detected by an automatic biochemical analyzer.The wet liver weight of mice was measured to calculate the hepato-somatic index.The expression of serine/threonine protein kinase(Akt),phosphorylated Akt (p-Akt) and mammalian target of rapmycin (m TOR) were detected by Western blot.Results Serum TG in normal group,model group and experimental group were (0.70±0.190),(0.97±0.19) and (0.86±0.14) mmol·L^(-1);TC in the three groups were(2.08±0.33),(3.59±0.32) and (3.03±0.32) mmol·L^(-1);LDL-C in the three groups were (0.26±0.04),(0.50±0.08) and (0.41±0.04) mmol·L^(-1);HDL-C in the three groups were (1.67±0.08),(2.47±0.24)and (2.67±0.30) mmol·L^(-1);the hepato-somatic index of three groups were 3.04±0.31,3.67±0.17 and3.29±0.23;the relative expression of Akt in the three groups were 0.78±0.11,1.38±0.18 and 0.86±0.08;pAkt in the three groups were 0.43±0.08,0.88±0.14 and 0.62±0.25;m TOR in the three groups were 0.80±0.05,1.85±0.23 and 1.16±0.17.Comparison between model group and normal group,the differences of the factors were statistically significant (all P<0.05).Comparison between experimental group and model group,the difference of TC,LDL-C,Akt and m TOR levels were significant (all P<0.05).Conclusion Resveratrol is efficient in attenuating high-fat diet induced hyperlipidemia in mice and this effect might be partly related to the inhibition of Akt/m TOR pathway.