从“脾主升清”理论探讨健脾益气法通过调控线粒体DNA甲基化相关酶改善妊娠母体亚临床甲减后代脑发育损伤的研究

妊娠期亚临床甲减（SCH）可导致后代神经智力发育异常，目前对是否补充LT4存疑，是近年内分泌领域关注的热点。研究表明SCH机体外周组织处于轻微的TH缺乏状态，TH是线粒体功能重要的调节激素，最新研究发现妊娠SCH妇女胎盘存在线粒体功能损伤，但这是否和胎儿脑发育异常有关，目前还尚缺乏从该角度去研究。我们前期研究证实健脾中药改善SCH脑MCT8蛋白表达，同时发现补中益气汤改善脑发育期线粒体MMT及ATP水平，因此推测妊娠SCH后代脑发育损伤的机制可能与脾虚线粒体功能损伤有关。为证实这一假说，我们建立妊娠SCH脾虚大鼠模型，采用分子生物学、基因测序等技术，分别从整体和细胞层次，观察mtDNA甲基化在脑发育中对线粒体功能、神经细胞分化的影响，及健脾益气中药改善情况。研究该病与脾虚mtDNA甲基化之间的关系及健脾益气中药的作用靶点，从而阐明妊娠SCH后代脑损伤发病机制，为从脾论治该病奠定基础。

Subclinical hypothyroidism (SCH) in pregnancy can lead to abnormal neurointellectual development in the offspring, and there are doubts about LT4 supplementation, which has been a hot topic of concern in the endocrine field in recent years. Studies have shown that the peripheral tissues of the SCH organism are mildly TH-deficient, an important regulator of mitochondrial function, and recent studies have found mitochondrial impairment in the placenta of pregnant SCH women. But whether this is related to fetal brain development abnormalities, there is a lack of research from that perspective. Our preliminary study confirmed that traditional Chinese medicine of Jianpi improved the expression of MCT8 protein in the brain of SCH, and also found that the MMT and ATP levels of mitochondria during brain development were improved by the tonifying Chinese medicine of Buzhong Yiqi, and therefore, it was hypothesized that the mechanism of brain developmental damage in the offspring of SCH during pregnancy might be related to the mitochondrial functional damage of spleen deficiency. In order to confirm this hypothesis, we will establish a gestational model of SCH in rats with spleen deficiency, and use molecular biology and gene sequencing techniques to observe the effects of mtDNA methylation on mitochondrial function and neuronal cell differentiation during brain development, as well as the improvement by the Chinese medicine of Jianpi Yiqi, and then to study the relationship between the disease and mtDNA methylation of spleen deficiency and the role of Chinese medicine of Jianpi Yiqi, so as to elucidate the pathogenesis of brain injury in the offspring of pregnancy with SCH and lay the foundation for treating the disease from the spleen theory.