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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。
Objective To investigate the effect and mechanism of antioxidant N-acetyl cysteine (NAC) on peripheral insulin resistance in high fat diet rats. Methods 8-week-old SD rats were randomly divided into normal diet group (NC group, n = 20), high fat diet group (HF group, n = 20) and hyperlipidemia + NAC group (n = 19). Feeding for 20 weeks. (1) plasma nitrotyrosine, malondialdehyde (MDA) and reduced glutathione (GSH) levels; (2) normal hyperglycemic insulin clamp test to assess the degree of peripheral insulin resistance; (3) The changes of IRS-1 mRNA and IRS-2 mRNA expression in muscle tissue of rats in each group were compared by real-time fluorescence quantitative PCR. Results (1) Plasma nitrotyrosine and MDA levels in HF group were significantly higher than those in NC group, GSH levels were lower than NC group, NAC could improve the above changes; (2) GIR in HF group was lower than that in NC group (P <0.01). After treatment with NAC, GIR was significantly improved (P <0.01). (3) The expression of IRS - 1 and IRS - 2 mRNA in muscle tissue of HF group decreased by 52.1% and 43.5% The expression of IRS-1 and IRS-2 in muscle tissue of NAC group increased by 73.8% and 68.4% compared with HF group (all P <0.01). Conclusion NAC intervention can improve insulin signaling in peripheral tissues and reverse the peripheral insulin resistance induced by high fat diet in rats. The mechanism may be related to NAC to correct the body’s oxidative and antioxidant imbalance.