【摘要】 目的探讨抗氧化剂N-乙酰半胱氨酸(NAC)对高脂饲养大鼠外周胰岛素抵抗的影响及机制。方法 8周龄SD大鼠随机分为正常饲料组(NC组,n=20)、高脂饲料组(HF组,n=20)和高脂+NAC组(NAC组,n=19)。饲养20周。(1)测血浆硝基酪氨酸,丙二醛(MDA)和还原型谷胱甘肽(GSH)水平;(2)正常血糖高胰岛素钳夹试验,评价外周组织胰岛素抵抗程度;(3)实时荧光定量PCR方法比较各组大鼠肌肉组织胰岛素受体底物-1(IRS-1)、胰岛素受体底物-2(IRS-2)mRNA表达的变化。结果 (1)HF组血浆硝基酪氨酸,MDA水平明显高于NC组,GSH水平低于NC组,NAC可以改善以上变化;(2)HF组葡萄糖输注率(GIR)比NC组降低(P<0.01),用NAC后GIR明显改善(P<0.01);(3)HF组肌肉组织IRS-1、IRS--2mRNA表达比NC组降低52.1%、43.5%(P均<0.01);NAC组肌肉组织IRS-1、IRS-2表达与HF组相比增加73.8%、68.4%(P均<0.01)。结论 NAC干预治疗能改善外周组织胰岛素信号传导,逆转高脂饲养导致的大鼠外周胰岛素抵抗,其机制可能与NAC纠正机体氧化及抗氧化失衡有关。更多还原

【Abstract】 Objective To study the changes of peripheral insulin resistance in high-fat-diet rat models and the effect of N-acetylcystein intervention.Methods 59 normal male SD rats aged 8 weeks were randomly divided into 3 groups:normal diet group（NC,n=20）,high fat diet group（HF,n=20）,and N-acetylcystein treated group (NAC,n=19,N-acetylcystein 300mg·kg^-1·d^-1and on high fat diet).At the end of twenty weeks feeding,we determined fasting plasma insulin （Ins）,glucose （Glu）and nitrotyrosine,malondialdehyde（MDA）,reduced glutathione hormone（GSH）.The glucose infusion rate （GIR）was measured by using euglycemic hyperinsulinemia clamp to evaluate the peripheral insulin resistance.The expressions of IRS-1,IRS-2 gene in muscle were detected by real time PCR.Results （1） The plasma insulin,glucose,nitrotyrosine and MDA concentrations were higher in HF group than in NC group,but GSH level in plasma was lower.NAC intervention could reverse these effects.（2）The GIR was decreased significantly in HF group as compared with NC group(5.25±1.2mg·min^-1·kg^-1vs 13.56± 1.7mg·min^-1·kg^-1)（P<0.01）,NAC intervention can reverse these effect(9.28±1.5mg·min^-1· kg^-1vs 5.25±1.2 mg·min^-1·kg^-1)（P<0.01）.（3）The gene expression of IRS-1 was decreased by 52.1% in HF group,and the expressions of IRS-2 was decreased by 43.5% （all P<0.01）.In contrast, the expressions of IRS-1,IRS-2 in NAC group were reversed by 73.8% and 68.4% respectively as compared with HF group （P<0.01）.Conclusions Antioxidant therapy could increase the gene expression of insulin signal transduction molecules in muscle,which might relate with the antioxidant effects of NAC.更多还原