【摘要】 目的:探讨早期高蛋白饮食对小于胎龄(SGA)大鼠糖代谢的影响及脂联素-AMP活化蛋白激酶(AMPK)信号通路在其中的作用。方法:孕期限食母鼠分娩的48只新生SGA雄性大鼠出生时随机分为SGA对照组(CS组)和SGA高蛋白组(HPS组)各24只;正常母鼠分娩的正常新生雄鼠24只为正常对照组(CN组)。CN组和CS组在3周哺乳期间母鼠予基础饲料自由饮食,断乳后幼鼠予基础饲料自由饮食至12周龄。HPS组在3周哺乳期间母鼠予高蛋白饲料自由饮食,断乳后幼鼠予高蛋白饲料自由饮食至4周龄,满4周龄予基础饲料自由进食至12周龄。4和12周龄时分别测定各组空腹血糖和胰岛素水平,计算胰岛素抵抗指数(HOMA-IR);测定血清脂联素水平;称取大鼠内脏脂肪质量(VFM),计算内脏脂肪体重百分比(VFM%);内脏脂肪组织切片测量脂肪细胞面积;检测骨骼肌AMPKα、磷酸化AMPKα和葡萄糖转运蛋白4(GLUT4)的表达。12周龄时各组行口服糖耐量试验(OGTT)。结果:4周龄各组HOMA-IR差异无统计学意义(P>0.05)。12周龄CS组HOMA-IR显著高于CN组和HPS组(均P<0.01),CN组与HPS组差异无统计学意义(P>0.05)。4和12周龄CS组VFM%、内脏脂肪细胞面积显著高于CN组和HPS组(均P<0.01),CN组与HPS组差异无统计学意义(P>0.05)。4和12周龄CS组血清脂联素水平、磷酸化AMPKα和GLUT4的表达低于CN和HPS组(P<0.05或P<0.01),CN组与HPS组差异无统计学意义(P>0.05),各组骨骼肌AMPKα的表达差异无统计学意义(P>0.05)。12周龄OGTT中CS组血糖下曲线面积高于CN和HPS组(均P<0.05),CN组与HPS组差异无统计学意义(P>0.05)。结论:早期高蛋白饮食干预能改善SGA大鼠的糖代谢,其机制与减少SGA内脏脂肪积聚、经由脂联素-AMPK信号通路上调骨骼肌GLUT4表达有关。更多还原

【Abstract】 AIM: To investigate the effect of early high-protein diet on glucose metabolism in small-for-gestational-age(SGA) rats and the role of adiponectin-AMP-activated protein(AMPK) signaling in this process.METHODS: Forty-eight neonatal male SGA rats were established by maternal food restriction throughout the period of pregnancy.The animals were randomly divided into SGA control group(CS group,24 rats) and high-protein intervention SGA group(HPS group,24 rats) when born.Twenty-four normal neonatal male rats were used as normal control group(CN group).The rats in CN group and CS group were breastfed for 3 weeks and their mothers were provided free access to basic diet.After weaning,they were provided free access to basic diet until 12 weeks of age.The rats in HPS group were breastfed for 3 weeks and their mothers were provided free access to high-protein diet.After weaning,they were provided free access to high-protein diet until 4 weeks of age.At the 4th week of age,they were provided free access to basic diet until 12 weeks of age.From 4 to 12 weeks of age,fasting blood glucose and insulin were measured and homeostasis model assessment of insulin resistance index(HOMA-IR) was calculated.The serum adiponectin level and the visceral fat mass(VFM) were detected.The percentage of VFM to body weight(VFM%) was calculated.The visceral fat was paraffin-embedded and the adipocyte area was determined.The expression of AMPKα,phosphorylated AMPKα(p-AMPKα) and glucose transporter 4(GLUT4) in skeletal muscle was analyzed.At the 12th week of age,the oral glucose tolerance test(OGTT) was performed.RESULTS: At the 4th week of age,no significant difference of HOMA-IR among groups was observed.At the 12th week of age,HOMA-IR in CS group was significantly higher than that in CN group and HPS group.No significant difference of HOMA-IR between CN group and HPS group was found.From 4 to 12 weeks of age,VFM% and adipocyte area of visceral fat in CS group were significantly higher than those in CN group and HPS group.No significant difference of VFM% and adipocyte area of visceral fat between CN group and HPS group was observed.The level of serum adiponectin,and the expression of p-AMPKα and GLUT4 in skeletal muscle were significantly lower in CS group than those in CN group and HPS group.The protein levels of p-AMPKα and GLUT4 were not significantly different between CN group and HPS group.No significant difference in the expression of AMPKα in skeletal muscle among groups was observed.At the 12th week of age,the area under the curve(AUC) of glucose level in OGTT was higher in CS group than that in CN group and HPS group.No significant difference of AUC of glucose level between CN group and HPS group was found.CONCLUSION: Early high protein diet may improve glucose metabolism in SGA rats,partly by avoiding excessive accumulation of visceral fat and possibly by activating adiponectin-AMPK signal pathway to increase GLUT4 expression.更多还原