慢性血栓栓塞性肺动脉高压（CTEPH）是一种以肺血管重塑为显著特点的致死性疾病。肺栓塞反复发作是其高危易患因素；内皮细胞凋亡，平滑肌细胞增殖是肺血管重塑的关键细胞学基础，深入探讨发病机制对寻找有效的肺动脉高压治疗方法有重要意义。研究证实当细胞内钙离子浓度升高时，利于NO合成限速酶eNOS的激活，促进NO生成，对血管内皮起到保护作用；去乙酰化酶SIRT1有同样作用；SIRTl的激活剂白藜芦醇（Resveratrol）可以抑制血管平滑肌的增殖。因此我们提出假说：Resveratrol上调SIRT1表达，通过调节[Ca2+]i变化影响eNOS-NO系统，在CTEPH血管重塑的发生发展中起保护性作用。本研究着眼于肺血管重塑这一影响CTEPH发展和预后关键点，在细胞水平通过建立过表达及基因干扰体系，利用多种研究手段探讨SIRT1在抑制CTEPH血管重塑过程中血管平滑肌增殖和改善内皮功能紊乱中的作用，并建立动物模型，从整体水平探讨Resveratrol作用机制以及与eNOS-NO的相互作用，寻找针对CTEPH患者有诊治价值的干预靶点，为CTEPH的治疗及新药开发提供新思路。

Chronic thromboembolism pulmonary hypertension (CTEPH) is a fatal complication with the predisposing factor of recurrent pulmonary embolism (PE). CTEPH is significantly characterized by pulmonary vascular remodeling with the key cellular basis of endothelial cells apoptosis and smooth muscle cells proliferation. Further insight of CTEPH pathogenesis is of important significances to new target in prevention and treatment of pulmonary hypertension. It has been suggested that the elevation of intracellular calcium concentration[Ca2+]i can promote the generation of NO (nitric oxide) activated by the key enzyme eNOS (endothelial nitric oxide synthase) and participate in the protection of vascular function. With the same function, Resveratrol, a SIRTl (silent information regulator 2-related enzymes 1) activator can inhibit the proliferation of vascular smooth muscle as well. On these grounds, we gain hypothesis: up-regulated expression of the SIRT1 by Resveratrol regulates eNOS-NO system with the change of intracellular calcium concentration, which may play a protective role of vascular remodeling in occurrence and development of CTEPH. This study will focus on the pulmonary vascular remodeling which is the critical point of CTEPH development and prognosis. We aim to explore the mechanism of SIRT1 in inhibiting vascular smooth muscle proliferation and improving endothelial dysfunction in the process of CTEPH vascular remodeling by the construction of Resveratrol and interference system at the cellular level, establishment of animal model to study the mechanism and interaction between Resveratrol and eNOS-NO at the model level. Our research will be helpful in seeking for interventions targeting and providing new ideas for treatment and the development of new drugs for CTEPH.