寻找有效的防治低氧肺动脉高压药物是重要的研究课题。我们前期研究发现中药成分红景天苷具有抑制在体大鼠低氧肺动脉高压的作用，并可上调腺苷2A受体(A2AR)表达，但具体机制不明；此外还发现A2AR基因缺失、线粒体途径凋亡减少与低氧性肺动脉高压的形成密切相关。据报道A2AR在冠脉能通过线粒体ATP敏感钾离子通道(MitoKATP)诱导细胞凋亡；红景天苷有线粒体保护功能。故本项目拟采用课题组前期已建立的A2AR基因敲除小鼠模型，在整体动物、离体细胞水平，利用膜片钳、共聚焦显微镜和分子生物学等技术，激动及阻滞MitoKATP，观察红景天苷对肺动脉高压、肺动脉平滑肌细胞增殖/凋亡、线粒体结构和膜电位、A2AR、MitoKATP的影响，研究红景天苷是否通过上调A2AR，阻滞MitoKATP开放，促进肺动脉平滑肌凋亡，减轻肺血管结构重建，抑制肺动脉高压，以期为开发新的防治低氧肺动脉高压的中药提供实验依据。

It's very important to find effective drugs to prevent hypoxia pulmonary hypertension. Our previous in vivo study shows that Salidroside, an ingredient of Chinese medicine can reduce pulmonary hypertension induced by hypoxia, and up-regulate the expression of A2AR, but the mechanisms remains unclear. Recent researches found that A2AR gene deletion and decrease of mitochondrial apoptosis are closed related to hypoxia pulmonary hypertension. Moreover, it was reported recently that A2AR can increase apoptosis through Mitochondrial ATP-sensitive potassium channel(MitoKATP) in coronary artery. Salidroside can protect mitochondrial has also been reported by researches. So in this study, we plan to use the technique of molecular biology, immunocyto-chemistry, confocal microscopy, patch clamp technique, electric microscopy, through both in vitro and in vivo study, using A2AR knockout mouse model we have established before, block and agitate MitoKATP, elucidate the effect of salidroside on A2AR and MitoKATP in pulmonary hypertension induced by hypoxia, and study the relationship between A2AR and MitoKATP in hypoxia pulmonary hypertension. In order to find out if Salidroside could reduce hypoxia pulmonary hypertension through up-regulate A2AR, inhibiting the opening of MitoKATP, increasing pulmonary artery smooth muscle cells ( PASMCs) mitochondria dependent apoptosis, and then inhibit the proliferation of PASMCs induced by hypoxia. The study will pay the way for finding a new way to treat pulmonary hypertension and cor pulmonale, and this study will provide experiment evidence for finding an effective traditional Chinese medicine to treat hypoxia pulmonary hypertension.