青年科学工作者论坛2008年第5期
硫辛酸对高脂膳食小鼠氧化应激与糖、脂代谢基因表达的影响
杨瑞丽 施用晖[1] 李武 岳鹏 乐国伟2
江南大学食品学院，无锡 214122
摘要：目的 探讨抗氧化剂硫辛酸(LA)对高脂膳食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)、三酰甘油(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(P<0.05)，TAC明显升高。LA显著降低血浆TG、TC、LDL–C和FPG、FINS的水平，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。
关键词：硫辛酸 氧化应激 基因芯片 糖代谢 脂代谢
中图分类号：R151.2 Q591 Q786 文献标识码：A
Effect of lipoic acid on gene expression related to oxidative stress, lipid metabolism and glycometabolism of mice fed a high fat diet
YANG Ruili, SHI Yonghui, LI Wu, YUE Peng, et al.
Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
Abstract：Objective To explore the effect of lipoic acid (LA) on oxidative stress, lipid metabolism and glycometabolism of mice fed with high fat diet (HFD). Methods C57BL/6 mice were randomly assigned to one of three groups (n=8).The control group consumed an ordinary diet. The other two experimental groups were fed with a high fat high diet, high fat plus 0.1% LA. Fasting plasma glucose, insulin, lipid level and antioxidant status were examined after 6 weeks. To investigate the molecular mechanisms underlying the effects of LA, we examined gene expression profiles in liver using 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 was a correlation 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, ß-oxidation and glycometabolism. Conclusions Treatment with LA improves 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.
Key word: lipoic acid, oxidative stress, gene expression, glucose metabolism, lipid metabolism
作者简介：杨瑞丽，女，博士研究生
1食品科学与技术国家重点实验室 江南大学
2通讯作者：乐国伟，男，教授，博士生导师