重组组织型纤溶酶原激活剂（rtPA）是缺血性脑卒中超早期最有效治疗药物，但会增加出血转化（HT）风险。我们前期研究发现connexin43(Cx43)参与HT。生物信息学分析表明lncRNAH19可通过microRNAs(miR-130a-3p、miR-301a-3p、miR-130b-3p)调控Cx43。经前期验证，动物模型中H19升高，细胞模型中下调H19致Cx43降低。据此我们提出假说，H19可能通过microRNAs调控Cx43参与HT。本研究拟建立Cx43+/-及野生型小鼠HT模型、氧糖剥夺/复氧复糖+rtPA细胞模型，采用RNAi、分子克隆、双荧光素酶和RIP等分子生物学技术，阐明H19是否通过调控Cx43参与HT、Cx43是否为H19下游靶点、H19是否通过microRNAs调控Cx43表达，逐步揭示H19作为上游分子调控Cx43的机制，为后续药物研究奠定基础。

Recombinant tissue plasminogen activator(rtPA) is the most effective drug for acute ischemic stroke in super early stage, but it can increase the risk of hemorrhagic transformation (HT). In previous experiment we have found that connexin43(Cx43) plays a role in HT. Bioinformatics analysis revealed that lncRNA H19 might regulate Cx43 via microRNAs(miR-130a-3p、miR-301a-3p、miR-130b-3p). We have proved that H19 increased in HT model and knock-down of H19 led to decrease of Cx43, which suggests that H19 might affect HT through regulating Cx43 via microRNAs. Cx43+/- and wild-type mice animal model of HT as well as oxygen and glucose deprivation /reoxygenation (OGD/R) and rtPA intervention cell model will be established. With the molecular biological techniques such as siRNA, molecular cloning, luciferase assay and RIP, this project intends to evaluate whether H19 functions in HT via Cx43, whether Cx43 is the downstream target of H19 and whether H19 regulates Cx43 via microRNAs. We hope to gradually reveal the roles of H19 on Cx43 as the upstream mechanism and lay the foundation for future drug development.