瘦素基因甲基化对孕鼠糖代谢变化的影响

Effect of leptin gene methylation on glucose metabolism in pregnant rats

目的探讨不同孕期小鼠体内孕激素、胰岛素、瘦素的动态水平及瘦素基因启动子区甲基化的变化特点,分析其相互关系及对孕期糖代谢的影响。方法将C57BL/6J孕鼠分为孕早期组、孕中期组、孕晚期组及产后7d组(每组5只),并取未孕的C57BL/6J雌鼠5只作为未孕组进行对照。测定各组空腹血糖及葡萄糖耐量情况,检测不同孕期血清中孕酮、胰岛素、瘦素水平以及瘦素基因启动子的甲基化水平。结果孕早、中、晚期组小鼠血清中胰岛素(分别为13.70±0.70、14.78±0.91、16.07±0.55mU/L)、孕酮(分别为10.10±0.37、11.41±0.50、15.34±0.65μg/L)、瘦素(分别为1356.73±100.41、1628.02±53.03、1954.12±39.71ng/L)均明显高于未孕组(分别为12.25±1.62mU/L,7.14±0.38μg/L,934.38±62.29ng/L)及产后组(分别为12.46±0.93mU/L,9.74±0.82μg/L,1259.19±105.74ng/L),不同孕期间比较差异均有统计学意义(P<0.01),但未孕组与产后组差异无统计学意义。孕期空腹血糖偏低,孕中、晚期小鼠注射葡萄糖后的血糖明显高于未孕组(P<0.01)。胎盘中瘦素基因启动子区的甲基化水平随妊娠进展降低。结论孕期孕激素、胰岛素和瘦素的高水平共同参与妊娠期生理性胰岛素抵抗的发生,使空腹血糖降低,糖耐量下降。正常妊娠期瘦素水平的变化与胎盘组织瘦素基因的甲基化水平有关。

Objective To examine the dynamic level of progesterone,insulin,and leptin,as well as the change in the features of leptin gene methylation in the promoter region of pregnant rats during different gestation stages and to analyze the correlation and effect of these conditions on glucose metabolism during gestation.Methods C57BL/6J pregnant rats are divided to four different groups,namely,early,mid-,and late gestation,as well as seven days postpartum（five rats for each group）.Five C57BL/6J non-pregnant rats are taken as the control group.The change in glucose metabolism during gestation was determined by measuring the glucose tolerance of rats in different groups and by testing the level of progesterone,insulin,and leptin in the sera and the level of the methylation of leptin gene promoters during different stages of gestation.Results The levels of insulin [（13.70±0.70,14.78±0.91,and 16.07±0.55）mU/L],progesterone [（10.10±0.37,11.41±0.50,and 15.34±0.65）μg/L],and leptin [（1356.73±100.41,1628.02±53.03,and 1954.12±39.71）ng/L] in pregnant rats in the three groups（early,mid-,and late gestation） are apparently higher than that of the non-pregnant rats [（12.25±1.62）mU/L,（7.14±0.38）μg/L,and（934.38±62.29）ng/L] and the postpartum group [（12.46±0.93）mU/L,（9.74±0.82）μg/L,and（1259.19±105.74）ng/L].The difference among the different stages of gestation has statistical significance（P〈0.01）,but the difference between the non-pregnant and postpartum groups is statistically insignificant.Fasting blood glucose during gestation is low.The level of blood glucose in mid-gestation and late-gestation rats after being injected with glucose is apparently higher than that of the non-pregnant group（P〈0.01）.The level of methylation in the leptin gene promoter zone of the placenta drops along with gestation.Conclusions High levels of progesterone,insulin,and leptin contribute to physiological insulin resistance during gestation,resulting in reduced fasting blood glucose and glucose resistance.The change in leptin levels during normal gestation is associated with the level of methylation of the leptin genes in placental tissues.