长期酒精摄入对大鼠骨骼肌组织IR、IRS-1和PI-3K基因表达的影响

Effect of chronic ethanol intake on insulin receptor,insulin receptor subsrate-1 and phosphoinositide 3-kinase mRNA expression in skeletal muscle of rats

目的研究酒精长期作用下对大鼠骨骼肌胰岛素受体(IR)、胰岛素受体底物-1(IRS-1)、磷脂酰肌醇3-激酶p85亚单位(PI-3K)mRNA表达的影响,探讨酒精与胰岛素抵抗的关系及相关分子机制。方法清洁级Wistar大鼠80只(雌雄各半),按体重随机分为对照组和低、中、高剂量组,分别给予蒸馏水以及10%、20%和33%酒精溶液,灌胃剂量为每天10ml/kgbw。第19周末,断头处死大鼠,测定空腹血糖和血胰岛素,计算HOMA胰岛素抵抗指数(HOMA-IR)。提取骨骼肌总RNA,通过RT-PCR测定IR、IRS-1、PI-3K(p85)mRNA表达水平。结果雄性大鼠,与对照组比较高剂量组空腹血糖,低、中剂量组空腹胰岛素水平升高,各酒精剂量组HOMA-IR指数均升高。IRmRNA的表达在中、高剂量组降低,而IRS-1、PI-3K(p85)mRNA表达水平表现为随着酒精剂量的增加先升高后降低,与对照组比较差异有显著性(P<0.05);与对照组比较,雌性大鼠高剂量组空腹血糖升高、空腹血胰岛素下降,IR、IRS-1、PI-3K(p85)mRNA的表达在中、高剂量组降低(P<0.05)。各剂量组HOMA-IR指数与对照组比较差异无显著性。结论长期摄入过量酒精可以造成骨骼肌组织IR、IRS-1、PI-3K(p85)mRNA表达的降低,这可能是酒精降低胰岛素敏感性,引起胰岛素抵抗的分子机制。

Objective To study the effect of chronic ethanol intake on insulin receptor （IR）, insulin receptor substrate-1 （IRS-1） and p85 subunit of phosphoinositide 3-kinase （PI-3K） mRNA expression in skeletal muscle of rats and explore the molecular mechanism of ethanol induced insulin resistance. Methods 80 Wistar rats were randomly divided into four groups on the basis of body weight： control （C） group, low（L）, moderate （M） and high （H） ethanol group. Each group was comprised of 10 male and 10 female rats. Rats were given ethanol in different concentration of （10%, 20% and 33% ） through intragastric-feeding and ethanol doses was 10ml/kg bw per day. After 19 weeks treatment, fasting plasma glucose and insulin were measured. HOMA-IR index of each group were calculated. The expression of IR, IRS-1 and PI-3K （p85） mRNA in skeletal muscle were detected by RT-PCR. Results In male rats, the fasting plasma glucose of group H, fasting plasma insulin of group L, M and HOMA-IR indexes of all ethanol-fed groups were higher than those of group C（P 〈 0.05）. The levels of iR mRNA of group L and H was lower, while increasing with the ethanol doses, IRS- land PI-3K（p85） mRNA expression increased first, then was decreased （ P 〈 0.05）. In female rats, in comparation with group C, the fasting plasma glucose of group H was higher, while fasting plasma insulin was lower, the levels of IR, IRS-1, PI-3K（p85） mRNA of group H and M were suppressed（ P 〈 0.05）. HOMA-IR indexes had on differences in the four groups of female rats （ P 〉 0.05）. Conclusion The present results suggested that chronic ethanol intake could induce insulin resistance and down-regulated the expression of IR, IRS-land PI-3K mRNA in skeletal muscle could be the molecular mechanism.