瘦素基因甲基化对孕鼠糖代谢变化的影响.docVIP

瘦素基因甲基化对孕鼠糖代谢变化的影响 辛静 黄金 通讯作者：李真 第三军医大学附属新桥医院妇产科（重庆 400037） 摘要 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变化特点，分析其相互关系及对孕期糖代谢的影响。方法：采用随机的方式取孕前、孕早期、孕中期、孕晚期及产后7天的雌鼠各五只，进行葡萄糖耐量的测定从而了解孕期糖代谢的变化，并测定不同孕期血清中孕酮、胰岛素和瘦素水平，以了解三者间的动态关系，通过检测瘦素基因启动子的甲基化水平进一步了解影响瘦素水平变化的机制。结果：孕鼠血清中胰岛素、孕酮、瘦素水平明显高于非妊娠期，并随孕期逐渐升高(P0.01)，孕期空腹血糖偏低，糖耐量较非孕期有降低的趋势，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，糖耐量下调。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。 关键词 妊娠；瘦素；胰岛素抵抗；糖代谢；甲基化 The effect of the leptin gene methylation on glucose metabolism in pregnant mice Xin Jing Huang Jin (Department of Obsterics and Gynecology， Xin Qiao Hospital，Third Military Medical University, Chong Qing 400037, China) Correspongding author: LI Zhen Abstract: [Purpose] To investigate the changes of progesterone, insulin and leptin in pregnant mice and the correlative mechanism among them, as well as the effects on the change of glucose metabolism. [Methods] Female mice were divided randomly to five different groups, non-pregnancy, early-gestation, mid-gestation, late-gestation and postpartum mice respectively, in order to identify the change of glucose metabolism during the whole duration of pregnancy. The levels of progesterone, insulin and leptin in different periods of pregnancy were measured to clarify the relationship among them. Also the level of methylation of the leptin promoter gene was detected to find out the mechanism of the change on the level of leptin. [Results] The serum levels of progesterone, insulin and leptin of pregnant mice are dramatically higher than that of the non-pregnant mice, and rising in accord with the development of pregnancy (P0.01). Fasting serum glucose in duration of pregnancy is lower and glucose tolerance stay in a decreasing tendency until the end of gestation. With the higher expression of leptin, methylation of the leptin promoter is reduced during gestational period. [Conclusion] High level of progesterone, insulin and leptin takes part in the physiological insulin res