【作者】 章静；

【导师】 胡刚；

【作者基本信息】 南京医科大学 ， 药理学， 2006， 硕士

【摘要】 Aquaporin-4基因敲除对CD1雌性小鼠生殖功能的影响及其机制研究 水通道蛋白(aquaporins，AQPs)是一类广泛存在于原核真核生物细胞膜上，选择性高效转运水分子的特异孔道，对机体的水平衡和细胞微环境的稳定发挥关键作用。迄今为止，经分子克隆发现的哺乳动物AQPs家族已有13个在蛋白质序列上有同源性的成员(AQP0～AQP12)。其中AQP4在脑内的表达最为丰富，主要表达于星形胶质细胞和室管膜上皮细胞，富集于朝向血管面、软脑膜面和神经突触的胶质细胞膜区。这种分布特点提示AQP4在维持脑内的内环境稳态中发挥重要作用，它可能是胶质细胞参与脑功能调节的重要结构基础。 AQP4在下丘脑弓状核(arcuate nucleus，ARC)和视前区(preoptic area，POA)的星形胶质细胞膜也有表达，ARC和POA是下丘脑神经内分泌系统中的重要区域，含有多种神经递质及肽类物质，其中促性腺激素释放激素(gonadotropin-releasing hormone，GnRH)主要调节垂体前叶的生殖内分泌功能。下丘脑-垂体-卵巢轴(hypothalamus-pituitary-ovary axis，HPOA)是影响雌性生殖能力的重要调控因素，在生殖功能中发挥主要的调节作用。GnRH神经元分泌GnRH，调节垂体中促性腺细胞分泌卵泡刺激素(follicle-stimulating hormone，FSH)和促黄体生成素(luteotrophic hormone，LH)，促性腺激素作用于性腺受体，引起性腺激素分泌并影响生殖功能。因此，位于下丘脑星形胶质细胞膜表面的AQP4可能通过调节星形胶质细胞的功能而影响GnRH神经元释放GnRH，继而调节下丘脑-垂体-卵巢轴，最终影响生殖功能。 有研究报道AQP4在大鼠的所有腺垂体组织包括嗜碱性、嗜酸性、嫌色腺细胞及滤泡星形细胞膜上均有表达，分布在这些部位的AQP4可能参与了激素释放的调节过程。因此，分布于嗜碱性内分泌细胞膜上的AQP4也可能直接调节FSH和LH的分泌过程，进而影更多还原

【Abstract】 The aquaporins (AQPs) are a family of small (~30 kDa/monomer), hydrophobic, integral membrane proteins that are expressed widely in the animal and plant kingdoms, 13 members having been identified so far in mammals. Their unique permeability characteristics and distribution in numerous tissues indicate diverse roles in the regulation of water homeostasis. Aquaporin-4 (AQP4) is a predominant water channel protein in mammalian brains. Studies aimed at determining the cellular distribution of AQP4 in the CNS have revealed that AQP4 protein expression is restricted to the ependymal cell lining of the ventricles and glial cell membranes, where the most abundant expression was found in perivascular glial processes. This pattern of distribution suggests that AQP4 may play a critical role in balancing the water homeostasis in the brain, and may be the important structural foundation of astrocytes in regulating brain functions.AQP4 is ubiquitously expressed in the hypothalamus, which is closely related to the neuroendocrine function, with a remarkable prevalence in periventricular areas (including preoptic region) and arcuate nucleus. At the same time, these two brain regions are importantly involved in neuroendocrine regulation of gonadotropin-releasing hormone (GnRH) neurons, which are controlled by astrocytes via different mechanisms including regulation of neuron communication, neurosecretion, and synaptic plasticity. GnRH is required for secretion更多还原