目的探讨硫辛酸(LA)对高脂饲料小鼠血糖、血脂代谢和抗氧化能力的影响。方法24只C57BL/6雄性小鼠,随机分为3组:即对照组(正常饲料),高脂组(高脂饲料),LA组(高脂饲料+0.1%LA),6周后测定空腹血糖(FPG)、胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)等糖脂代谢指标以及丙二醛(MDA)、超氧化物歧化酶(SOD)和总抗氧化能力(TAC)等抗氧化指标,同时用Affymetrix MOE430A基因芯片分析肝脏抗氧化、糖脂代谢相关功能基因的表达。结果与高脂组相比,LA组MDA含量显著降低,TAC明显升高(P〈0.05)。LA显著降低血浆TG、TC、LDL-C和FPG、FINS的水平(P〈0.05),MDA含量与HDL-C/TC(r=-0.47,P〈0.05)和胰岛素抵抗指数(r=0.74,P〈0.05)显著相关。硫辛酸改变高脂组自由基/氧化应激、糖脂代谢相关通路大部分响应基因的表达水平。结论高脂引发氧化-抗氧化系统失衡,硫辛酸通过直接清除自由基以及恢复自由基/氧化应激通路相关基因的表达水平解除氧化应激而有助于防治高脂引发的糖脂代谢紊乱。
Objective To explore the effect of lipoic acid(LA) on oxidative stress,lipid and glucose metabolism of mice fed with high fat diet(HFD).Methods C57BL/6 mice were randomly assigned to three groups(n=8).The control group were administrated with an ordinary diet.The two experimental groups were fed with a high fat diet,high fat plus 0.1% LA.Fasting plasma glucose,insulin,lipid level and certain antioxidant indexes were examined after 6 wk.The gene expression profiles in liver were examined by the GeneChip microarray system.Results Hyperlipidemia and glycometabolism disorders,accompanied by a depressed antioxidant defense system,were observed in HFD-fed mice.These changes were partially restored in the LA-treated group.There were correlations between MDA and the ratio of HDL-C/TC(r=-0.47,P〈0.05),homeostasis model assessment(HOMA) index(r=0.74,P〈0.05).DNA microarray analysis of liver showed that LA ingestion up-regulated the expression of genes related to free-radical scavenger enzymes,β-oxidation and glycometabolism.Conclusion LA could improve insulin resistance and hyperlipidemia associated with HFD feeding in mice.The mechanism may involve preventing oxidative stress by scavenging reactive oxygen species(ROS) directly and increasing those of free-radical scavenger enzymes genes expression indirectly.