AMPK在子痫前期中的作用

发布时间：2018-02-01 11:33

本文关键词： 子痫前期 AMPK HTR8/SVneo 代谢组学　出处：《重庆医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：背景:子痫前期(Preeclampsia,PE)是一种常见的妊娠期特有疾病,是引起母胎发病和死亡的重要原因,其发病原因和机制研究甚多,但不明确,可能涉及胎盘、胎儿和母体多方面因素。研究显示绒毛外滋养细胞侵袭不足,子宫螺旋动脉重铸障碍,导致胎盘缺血缺氧是子痫前期重要的病理特征,因此子痫前期又被称为是胎盘缺血性疾病。AMPK是生物能量代谢调节的关键分子,在多种代谢性疾病中通过调节葡萄糖摄取和脂肪酸代谢发挥重要作用。因此我们通过研究子痫前期代谢组学变化,检测相关代谢通路生物分子变化探究子痫前期的病理机制,为临床预测及治疗提供依据。方法:收集正常孕妇及子痫前期孕妇胎盘组织,建立细胞模型,GC-MS进行代谢组学分析,q-PCR和Western Blotting检测相关基因及蛋白表达;MDA检测脂质氧化水平;ACEA实时细胞计数仪及transwell检测滋养细胞的迁移侵袭能力。结果:子痫前期孕妇胎盘组织代谢组学发生改变(p0.05),AMPK磷酸化水平明显升高(N=16,p0.05);成功建立子痫前期体外细胞模型,缺氧上调滋养细胞AMPK表达(N=6,p0.05),抑制滋养细胞迁移侵袭能力,改变滋养细胞的代谢组学。结论:子痫前期孕妇代谢失衡;缺氧时滋养细胞优先利用短链脂肪酸;缺氧激活AMPK进而抑制滋养细胞的迁移侵袭能力。
[Abstract]:Background: Preeclampsiaena preeclampsis (PEI) is a common gestational disease and an important cause of maternal and fetal morbidity and mortality. The etiology and mechanism of preeclampsis preeclampsis (PEP) is much studied, but it is not clear and may involve placenta. Fetal and maternal factors. Studies have shown that inadequate invasion of extravillous trophoblast and dysplasia of uterine spiral artery lead to placental ischemia and hypoxia as an important pathological feature of preeclampsia. Therefore, preeclampsia is also called placental ischemic disease. AMPK is a key molecule in the regulation of biological energy metabolism. It plays an important role in many metabolic diseases by regulating glucose uptake and fatty acid metabolism. Therefore, we explore the pathological mechanism of preeclampsia by studying the changes of preeclampsia metabolomics and detecting the biomolecular changes of related metabolic pathways. Methods: the placental tissues of normal and preeclampsia pregnant women were collected. In order to establish a cell model, GC-MS was used to detect the expression of related genes and proteins by Western Blotting. ACEA real-time cell counter and transwell were used to detect the migration and invasion ability of trophoblastic cells in preeclampsia. The changes of placental tissue metabolism in pregnant women showed that the level of AMPK phosphorylation in placenta of pregnant women was significantly increased, and the in vitro cell model of preeclampsia was successfully established. Hypoxia upregulated the expression of AMPK in trophoblast, inhibited the migration and invasion of trophoblast and changed the metabolism of trophoblast. Conclusion: the metabolic imbalance of preeclampsia pregnant women, trophoblast preterm preeclampsia preferentially uses short chain fatty acid. Hypoxia activates AMPK and inhibits trophoblast migration and invasion.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R714.244

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