孕鼠大量酒精摄入对子代胰岛素敏感性及脂肪源性细胞因子的影响

目的观察孕期大量摄入酒精对子代成年期胰岛素敏感性影响并探讨其影响机制。方法6只SD孕鼠随机分为对照组和酒精组,酒精组以酒精灌胃(4g·kg-1·d-1)至分娩前。第16周龄子代鼠进行静脉葡萄糖耐量试验(IVGTT),RT-PCR检测脂肪组织瘦素、抵抗素及脂联素mRNA表达水平,放射免疫方法测血清瘦素、抵抗素及脂联素含量。结果出生时,酒精组新生鼠体重低于对照组(5.7g±0.1gvs6.9g±0.1g,P<0.01);16wk龄时,与对照组比较,酒精组子代16wk龄时,血糖曲线下面积增加(P<0.05)、8min时葡萄糖刺激的胰岛素分泌增加(P<0.01)、胰岛素敏感指数(SI)及葡萄糖耐量指数(KG)降低(P<0.01);脂肪组织中抵抗素mRNA表达及血清抵抗素水平增加(P<0.05),而脂肪组织中瘦素、脂联素mRNA表达及血清瘦素和脂联素水平均无变化。结论孕期大量饮酒可引起后代宫内发育迟缓,并导致其成年期发生胰岛素抵抗,其机制部分与脂肪组织抵抗素表达增加有关。

Effect of maternal ethanol consumption during gestation on insulin sensitivity and adipokines in the rat offspring

Aim To investigate the effect of prenatal alcohol on insulin sensitivity of rat offspring and its underlying mechanism. Methods Female Sprague Dawley rats were given ethanol 4 g·kg-1·d-1 by gavage throughout pregnancy. At 16 wk of age, the rat offsrping underwent intravenous glucose tolerance test. The mRNA level of adipose leptin, resistin and adiponectin were determined by RT-PCR. Serum leptin, resistin and adiponectin were measured with RIA kits. Results Newborn ethanol rats had lower birth weight than control (5.7±0.1) g vs (6.9±0.1) g,P<0.001]. Compared with control, at 16 wk of age, ethanol rat offspring appeared impaired glucose tolerance. The area under glucose curve was significantly greater (1030±80 ) mmol·L-1·min-1vs(789±32) mmol·L-1·min-1,P<0.05]. Acute insulin response to glucose was significantly increased (2020±881) pmol·L-1 vs (406±37) pmol·L-1,P<0.01]. Insulin sensitivity index and glucose tolerance index were significantly decreased (P<0.001,P<0.01), and glucose effectiveness was not different between groups. Adipose resistin mRNA and serum resistin concentration were elevated, but adipose leptin and adiponectin mRNA, serum leptin and adiponectin level were normal. Conclusion Heavy ethanol consumption during pregnancy induces intrauterine growth restriction, resulting in insulin resistance in rat offspring by increasing resistin mRNA and protein.