孕期及哺乳期大豆异黄酮干预对子代大鼠肥胖的影响及其机制研究

Obesity has become overwhelmed all over the world. It estimates that there are more than 3.28 billion overweight and obese individuals by 2030. Isoflavone is a kind of phytoestrogen. Research showed that isoflavone could protect people from oxidation, cancer, osteoporosis, cardiovascular disease, etc. The present research aims to investigate the effect of maternal isoflavone protection rats offspring from obesity and its mechanism from the pint of view of its body weight reduction effect. 8-week-old Wister pregnant rats are randomly assigned to 6 groups which contains different dosage groups and control groups. Rats are given different dosage of isoflavone during duration of pregnant and lactation. Offspring of rats are induced to obesity with high fat diet and killed by the age of 6 month. The effect of isoflavone on the productive system of offspring will be observed. Furthermore, epigenetics methods are used for detection of DNA methylation of organs and blood, which reveals the machanism of preventive effect of isoflavone on offspring obesity. The research is highly advanced innovative project. The results of this research will provide a preventive measure to conquer obesity and a basis evidence for the new bioactivity of isoflavone to exploit.

肥胖在全球的迅速蔓延之势已势不可挡。据估计到2030年全球超重和肥胖患者超过32.8亿。大豆异黄酮是一类植物雌激素，研究表明大豆异黄酮具有抗氧化、抗癌、预防骨质疏松症、预防心血管疾病、改善妇女更年期症状、抗衰老等诸多生理功能。本研究从大豆异黄酮抑制体重增加作用出发，观察孕期及哺乳期母体大豆异黄酮干预对子代大鼠肥胖的影响，并探讨其可能的机制。8周龄Wister雌性大鼠受孕后随机分为6组，分别为不同剂量的大豆异黄酮组及相应的对照组。母鼠在孕期及哺乳期均给予不同剂量的大豆异黄酮，子鼠断乳后高脂饲料喂养诱导肥胖至6月后处死。观察大豆异黄酮对子代大鼠生殖系统的影响，表观生物学实验检测各组织和血液中肥胖和食欲相关因子的甲基化情况，确定孕期及哺乳期大豆异黄酮干预对子代大鼠肥胖的影响及其可能机制。该项目属于前沿性创新课题，将为肥胖的预防开创新的领域，也为大豆异黄酮的新生物活性的开发提供实验室依据。

目的：探讨母体孕期及哺乳期大豆异黄酮干预对子代大鼠肥胖和生殖的影响及其可能的机制。方法：选用性成熟雌性大鼠，受孕后在孕期及哺乳期间均给予不同剂量的大豆异黄酮（本研究中选取大豆异黄酮的主要成分-金雀异黄素GEN作为受试物），并设立对照组。实验期间观察母鼠的体重生长情况；子鼠的体重生长及发育情况；取母鼠和子鼠的各脏器称重，计算脏体比；检测子鼠血液中各种生化指标、激素以及炎性因子的水平；观察子鼠生殖系统的病理改变；BSP法观察子鼠下丘脑组织中leptin receptor (Lepr)甲基化情况，以及脂肪组织中peroxisome proliferator-activated receptor gamma(Pparγ)，CCAAT/enhancer binding protein alpha (Cebpα)的甲基化情况。结果：研究发现（1）孕期及哺乳期高剂量GEN干预可以显著降低母鼠及子鼠的体重；增加子鼠子宫及卵巢的脏体比；升高子鼠血糖水平；（2）孕期及哺乳期低剂量GEN干预对母鼠及父鼠各项指标均无显著性影响；（3）孕期及哺乳期低剂量GEN干预可以显著增加子鼠的体重及脂肪的脏体比，并增加雄性子鼠的摄食量；同时升高子鼠血脂水平，影响生化指标及激素水平；促使子宫内膜增生；（4）孕期及哺乳期低剂量GEN干预可以显著降低雄性子鼠下丘脑Lepr甲基化程度，增加Ppar甲基化程度。结论：孕期及哺乳期低剂量大豆异黄酮干预可以显著影响子鼠的肥胖和生殖。