七氟醚通过miRNA218-NF-κB信号通路调节胚胎干细胞向神经元分化的分子机制研究

People pay more attention to affection of fetal nervous system development of early pregnant women caused by clinical commonly used anesthetics sevoflurane. Research shows that sevoflurane can damage learning and memory function of early pregnant mice offspring. Our study also finds that sevoflurane reduces the embryonic stem cell self-renewal capacity and causes cells differentiation in advance via up-regulation of miRNA218 and down-regulation of NF-κB expression. Early differentiated embryonic stem cells induce incomplete ectodermal differentiation during the course of differentiation into neurons, leading to abnormal development of neural stem cells and neurons. We therefore hypothesize that sevoflurane can influence neuronal development and thus impair learning and memory function through miRNA218-NF-κB pathway. We intend to establish model of embryonic stem cultured in vitro and induce its differentiation into neurons, treat early pregnant mice with sevoflurane at the same time and analyze the affection of sevoflurane on neuron development by conditional over-expression or knockdown of miRNA218 and NF-κB in vitro and in vivo. We also would like to study its molecular mechanism in detail, provide the basis for the anesthetic drugs and anesthetic selection of early pregnant women receiving general anesthesia, and decrease the damage of anesthesia on the development of fetal nervous system.

临床常用的吸入麻醉药七氟醚对孕早期妇女胎儿神经系统发育的影响越来越引起大家的关注。研究表明，七氟醚能损害孕早期小鼠子代的学习和记忆功能，我们的研究也发现七氟醚通过上调miRNA218引起NF-κB表达下调从而降低胚胎干细胞自我更新能力，导致细胞提前分化；提前分化的胚胎干细胞在分化成为神经元过程中引起外胚层分化的不完全，最终导致神经干细胞和神经元发育异常。所以我们推测：七氟醚通过miRNA218-NF-κB通路影响神经元发育从而损害学习和记忆功能。我们拟通过建立体外培养胚胎干细胞并诱导其向神经元分化的模型，同时使用七氟醚麻醉孕早期小鼠，通过体内和体外条件性过表达或敲低miRNA218及NF-κB，研究七氟醚对神经元发育过程的影响，并进一步探讨其分子机制，为孕早期妇女接受手术需要全身麻醉时麻醉药物和麻醉方式的选择提供理论依据，降低麻醉对胎儿神经系统发育的影响。

临床常用的吸入麻醉药七氟醚对孕早期妇女胎儿神经系统发育的影响越来越引起大家的关注。研究表明，七氟醚能损害孕早期小鼠子代的学习和记忆功能，我们的研究也发现七氟醚可以降低胚胎干细胞自我更新能力，导致细胞提前分化；提前分化的胚胎干细胞在分化成为神经元过程中引起外胚层分化的不完全，最终导致神经干细胞和神经元发育异常。所以我们推测：七氟醚影响神经元发育从而损害学习和记忆功能。我们拟通过建立体外培养胚胎干细胞并诱导其向神经元分化的模型，同时使用七氟醚麻醉孕早期小鼠，通过体内和体外条件性过表达或敲低相关基因，研究七氟醚对神经元发育过程的影响，并进一步探讨其分子机制，为孕早期妇女接受手术需要全身麻醉时麻醉药物和麻醉方式的选择提供理论依据，降低麻醉对胎儿神经系统发育的影响。