长期酒精作用对大鼠骨骼肌PI-3K表达的影响

目的:研究酒精长期作用下对大鼠骨骼肌磷脂酰肌醇3激酶(phosphatidylinositol 3-kinase,PI-3K)调节亚基p85αmRNA及蛋白水平表达的影响,探讨酒精引起胰岛素抵抗的相关分子机制。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%、33%酒精溶液,灌胃剂量为10ml/(kg·bw·d)。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)。分离骨骼肌,通过RT-PCR和Westernblot方法测定p85αmRNA和蛋白表达水平。结果:雄性大鼠高剂量组空腹血糖,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。p85αmRNA及蛋白表达水平表现为随着酒精剂量的增加先升高后降低;雌性大鼠高剂量组空腹血糖升高、空腹血胰岛素下降,p85αmRNA及蛋白的表达在中、高剂量组降低。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p85α表达的改变,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。

EFFECT OF CHRONIC ALCOHOL INTAKE ON EXPRESSION OF PHOSPHATIDYLINOSITOL 3-KINASE IN SKELETAL MUSCLE OF RATS

Objective:To study the effect of chronic alcohol intake on expression of PI-3K-p85α (p85 regulatory subunit of phosphatidylinositol 3-kinase) in skeletal muscle of rats and explore the molecular mechanism of alcohol induced insulin resistance. Method:Eighty Wistar rats were randomly divided into four groups:control (C) group, low (L), moderate (M) and high (H) alcohol group. Each group was comprised of 10 male and 10 female rats. Rats were intragastrically given 10ml/(kg?bw?d) (10%, 20% and 33% alcohol solution) . Ninetteen weeks later, fasting plasma glucose and insulin were measured. HOMA-IR index of each group was calculated. Expression of p85αin skeletal muscle was detected by RT-PCR and Western blot. Results:In male rats, the fasting plasma glucose of group H, fasting plasma insulin of group L, M and HOMA-IR index of all alcohol-fed groups were higher than those of group C. With the alcohol doses increase, p85αmRNA expression and protein content increased first, then decreased. In female rats, the fasting plasma glucose of group H was the highest, while fasting plasma insulin was the lowest, and the expression of p85αof group H and M was suppressed(P<0.05). HOMA-IR index had no differences in the four groups of female rats. Conclusion:Chronic alcohol intake could change the expres-sion of PI-3K –p85 α in skeletal muscle and this may be the molecular mechanism of alcohol induced insulin resistance.