组蛋白乙酰化-miRNA（miR-671/miR-483-5p）环路调控海马神经元树突棘重塑在孕晚期母体接受丙泊酚麻醉手术致子代大鼠学习记忆损害中的作用

孕晚期有相当部分孕妇接受非产科手术，其对子代学习记忆的影响及机制不清楚。课题组前期发现丙泊酚对子代学习记忆的损害与海马区组蛋白乙酰化、树突棘形态学改变有关，手术加剧其损害。预实验显示孕晚期母体接受丙泊酚麻醉手术可致子代miR-671、miR-483-5p表达失调，其靶基因与神经发育、组蛋白替换密切相关。现已知组蛋白乙酰化与miRNA之间存在相互作用。据此我们提出假说“孕晚期母体接受丙泊酚麻醉手术通过组蛋白乙酰化-miRNA（miR-671/miR-483-5p）环路调控树突棘重塑损害子代大鼠学习记忆”。本项目拟观察孕晚期母体接受丙泊酚麻醉手术对子代组蛋白乙酰化-miRNA（miR-671/miR-483-5p）环路及其靶基因Ptma等表达、树突棘形态学、突触可塑性、学习记忆的影响，并通过干预组蛋白乙酰化、miR-671、miR-483-5p表达进一步验证假说。对子代学习记忆损害防治有意义。

There are many of pregnant women have to experience non-obstetrical surgery during gestation. The effect and the underlying mechanisms of the surgery on the learning and memory in offspring are unknown. Our preliminary study indicated that the memory impairment caused by maternal propofol anesthesia is associated with the inhibition of histone acetylation and the remodeling of neuronal dendrite spine in offspring rats’ hippocampus. Surgery deteriorates these changes caused by maternal propofol anesthesia. Our preliminary study results showed that maternal surgery under propofol anesthesia during late pregnancy resulted in miR-671 upregulation and miR-483-5p downregulation in offspring rat’s hippocampus. Their target genes are closely related with neuronal development and histone exchange. It is well known that histone acetylation and miRNAs interact with each other in regulating the expression of target genes’. Therefore, we hypothesise that “Maternal surgery under propofol anesthesia during late pregnancy impairs rat offspring’s learning and memory by remodeling hippocampal neuronal dendrite spine via interfering histone acetylation-miRNA （miR-671/miR-483-5p）circuit ”. In present study, the changes of histone acetylation, the expression levels of miR-671, miR-483-5p, their target genes Ngfr、Nrp2、Adgrl2 and Ptma , neuronal dendrite spine’s morphology and synaptic plasticity in offspring rats’ hippocampus caused by maternal abdominal surgery under propofol anesthesia during late pregnancy will be investigated. Furthermore, histone acetylation and the expression of miR-671 and miR-483-5p will be intervened respectively and the interfering effects on histone acetylation, the expression levels of miR-671 and miR-483-5p and their target genes, neuronal dendrite spine’s morphology, synaptic plasticity in offspring rats’ hippocampus and their learning and memory will be further investigated to test the hypothesis. The results of present study will give a highlight to the prevention and therapy for the learning and memory impairments in offspring.