高肺血流性肺动脉高压是左向右分流型先天性心脏病最常见的并发症，其发生机制尚不明确。研究认为钙激活性氯离子通道（CaCC）在调节肺动脉平滑肌细胞收缩及血管张力中起重要作用，我们的研究也显示CaCC通过调控肺血管重塑及细胞增殖参与了肺动脉高压的发生。进一步研究发现，CaCC的分子基础可能为跨膜蛋白16A（TMEM16A)。由此我们提出假说：TMEM16A可能表达于高肺血流性肺动脉高压大鼠的肺动脉平滑肌上，参与CaCC的调控、血管张力的调节及肺动脉高压的发生。本实验拟通过建立高肺血流性肺动脉高压大鼠模型，应用siRNA干扰、细胞转染、免疫组化、膜片钳等方法，旨在获得TMEM16A介导CaCC参与调控高肺血流性肺动脉高压大鼠肺动脉压力的可靠证据。本项目将阐明TMEM16A介导CaCC对高肺血流性肺动脉高压的调控机制，为确立TMEM16A作为高肺血流性肺动脉高压防治的新靶点提供更充分的科学依据。

Pulmonary hypertension induced by high pulmonary blood flow is the common complication of congenital heart disease induced by left-to-right shunt. The pathogenesy of PAH still has not totally been illuminated. It has been studied that calcium activated chloride channel (CaCC) plays a significant role in regulating the contraction of pulmonary smooth muscle cells(PASMCs) and the tension of pulmonary artery. Our researches have preliminary found that CaCC is involved in regulating the vascular structure remodeling, cell proliferation and the final pathogenesis of PAH. Recently transmembrane protein 16A(TMEM16A) is futher reported to be candidate of the molecular basis of CaCC. So we presume that TMEM16A probably expresses in PASMCs and functions to regulate CaCC, vascular tone and the pathogenesis of of PAH. in order to obtain the reliable evidences, we are going to establish animal model of PAH induced by high pulmonary blood flow. siRNA interference, cell transfection, immunohistochemistry and patch clamp technologues are adopted to explore the role of TMEM16A during the process of high pulmonary blood flow induced PAH. Finally, we are going to demonstrate on the role of TMEM16A during the process of high pulmonary blood flow induced PAH by mediating CaCC. it will provide with more sufficient scientific supports for TMEM16A as the new target spot in prevention and treatment of PAH induced by high pulmonary blood flow.