腺苷与肺动脉高压关系密切，可通过A2a受体抑制肺动脉高压形成。本课题组发现A2aR基因敲除小鼠出现肺动脉平滑肌细胞增殖、胶原沉积，低氧时更明显，但机制不明。近年报道内皮细胞在一定条件下可转变为平滑肌样细胞，即发生内皮-间充质转变（EndMT），并由TGF-β/Smads信号通路调控；体外实验发现缺氧时，肺小动脉内皮细胞可转分化成平滑肌样细胞，即EndMT可能参与肺血管重建。另报道在肾小球肾炎大鼠中激活A2aR可抑制EndMT。故本项目拟在整体、细胞和分子水平研究EndMT在A2aR基因敲除小鼠肺血管重建中的作用。此外,据报道积雪草具有增加腺苷产生的可能,本课题组已发现积雪草苷可改善低氧大鼠肺血管重建，并在体外实验中发现积雪草苷能抑制EndMT,故本项目采用A2aR基因敲除小鼠进一步探明积雪草苷的作用机制，以期找到一种安全有效、作用明确的治疗肺动脉高压药物。

The relationship between adenosine and pulmonary hypertension is always highly concerned. It has been reported that A2aR activation could reduce pulmonary hypertension induced by hypoxia. Our previous study shows that under chronic hypoxic conditions, proliferation of pulmonary artery smooth muscle cells and collagen deposition in A2aR knockout mice were more significant than those in wild mice. However, the mechanism is unclear. In recent years, it was found that endothelial cells can be transformed into smooth muscle-like cells under certain condition, namely endothelial-mesenchymal transition (EndMT), which was regulated by TGF-β/Smads. Previous study found that hypoxia induced the transdifferentiation of porcine pulmonary arterial endothelial cells into smooth muscle-like cells ,which indicated a potential role of EndMT in pulmonary vascular remodelling. Another report is that A2aR activation prevented progressive kidney fibrosis in a model of immune-associated chronic inflammation by inhibiting the development of EndMT. Therefore, this project intends to study the role of EndMT in pulmonary vascular remodelling induced by hypoxia in A2aR knockout mice through in vitro and in vivo study on the whole, cellular and molecular levels. We have already found that asiaticoside can reduce the hypoxic pulmonary arterial hypertension of rats , reverse pulmonary arterial remodeling, and inhibit EndMT in vitro. Based on the findings above, the project intends to make sure the effects of asiaticoside on hypoxic pulmonary hypertension in A2aR knockout mice expecting to find a drug with good efficacy and little side effect to treat pulmonary hypertension.