妊娠期高血压疾病(HDCP)是以全身小动脉痉挛致血管内皮广泛损伤为主要特征的一过性血压升高的慢性炎症性疾病，是否通过炎症和脂代谢交叉靶基因FABP4 DNA甲基化异常引起HDCP未见报道,前期研究发现HDCP中不同基因DNA高低甲基化并存, 且miRNAs是基因表达调控重要方式，提示存在更深层次调控机制,因此本项目拟复制HDCP动物模型，实时PCR等分析胎盘中FABP4的变化，在细胞中使其沉默和过表达，验证其在HDCP中作用；高通量MethyLight法等检测胎盘组织中FABP4 DNA甲基化和DNMTs等调控因子变化，阐明HDCP中DNA甲基化的作用机制，采用RNA干扰等阻断策略确定关键靶点；运用微阵列技术筛选HDCP特异性miRNAs，转染miRNAs抑制物表达载体和携载DNMTs重组质粒，探讨特异性miRNAs靶向调控DNMTs的机制，确定关键靶点，为HDCP靶向治疗提供理论依据。

Hypertensive disorder complicating pregnancy(HDCP) is a chronic inflammatory disease whose clinical manifestation is a transient increase of blood pressure in pregnancy. Its main feature is extensive vascular endothelial damages caused by systemic small artery spasm. However, it has not been reported that if HDCP is caused by DNA methylation aberration of FABP4 which is the cross-target gene between inflammation and lipid metabolism. Preliminary studies have found that hypermethylation and hypomethylation co-exist in different genes of HDCP, and miRNAs is an important way of gene expression regulation, which suggest the existence of a deeper level regulation mechanism. Thus this project intends to copy the HDCP model, uses real-time PCR and so on to detect the changes of FABP4 in placenta, and verifies its effects in HDCP by its silence and over-expression in cells. The changes of FABP4 DNA methylation and regulatory factors such as DNMTs in placenta are detected by high-throughput MethyLight assay in order to clarify the DNA methylation mechanism in HDCP, and to determine the key targets by using block strategies such as RNA interference. To screen HDCP-specific miRNAs by using microarray analysis. Transfecting miRNAs inhibitor expression vector and the recombinant plasmidand carrying DNMTs. This project seeks to explore the targeted regulation mechanism of DNMTs through specific miRNAs and to identify the key targets so as to provide a theoretical basis for the targeted therapy of HDCP.