右心重塑、衰竭是肺动脉高压（PAH）预后的关键决定因素，炎症反应影响PAH及其导致的右心重塑和衰竭的程度。课题组前期通过转录组分析发现Dectin-1在PAH小鼠右心室表达显著增加，Dectin-1敲除减轻右室心肌肥厚和纤维化程度，同时炎症小体活化产物IL-1β和IL-18表达减少。但Dectin-1在PAH致右室重塑和心力衰竭中的作用机制尚不清楚。为了验证本研究的科学假说“PAH损伤右心室心肌细胞释放可活化Dectin-1的配体，激Dectin-1依赖的炎症小体的形成，促进右心室炎症反应，加剧心室重构和心力衰竭”，拟使用Dectin-1和NLRP3敲除小鼠制作PAH致右室重塑模型，结合体外细胞共培养、骨髓移植等方法重点明确PAH激活心脏Dectin-1的分子机制，明确Dectin-1依赖的炎症小体活化对右心室重塑和心力衰竭的作用机制，从而为提高PAH治疗的预后提供新思路。

Right ventricular remodeling and dysfunction is a key prognosis effector of pulmonary hypertension. Inflammatory response modulates the degree of PAH and PAH induced right ventricular remodeling and dysfunction. Our preliminary studies suggested that receptor Dectin-1 was up-regulated in right ventricular of PAH mouse, Dectin-1 deficiency mouse exhibited attenuated cardiac hypertrophy and fibrosis, accompanied with decrease IL-1β and IL-18, which is the activationproduction of inflammasome. However, the exact mechanism of Dectin-1 on Right ventricular remodeling is still unknown. In this project, we hypothesis that cardiomyocyte injured by PAH could release the activator of Dectin-1, which further promote the activation of Inflammasome to increase inflammatory response of the right ventricular, Dectin-1 promotes right ventricular remodeling and dysfunction after PAH. To verify this hypothesis, we will use Dectin-1-/- mouse and Nlrp3-/- mouse in vivo, bone marrow transplantation, RNA-seq and cells co-culture in vitro to reveal the molecular mechanism of Dectin-1 and inflammasome in right ventricular remodeling and dysfunction after PAH. Our research will provide the novel ideals and experimental basis for the prognosisimprovement of PAH therapy.