肺血管重构是左心衰竭相关性肺动脉高压(pulmonary hypertension due to left heart failure , PH-LHF)发病机制的核心。内皮素-1及白介素-6是肺血管重构重要的诱导因子。信号转录子和转录激活子3（STAT3）/活化T细胞核因子（NFAT）信号通路过度激活参与细胞增殖与凋亡失平衡，推测其在PH-LHF肺血管重构中起重要作用。已知脱氢表雄酮（dehydroepiandrosterone, DHEA）可有效抑制肝细胞及外周血管平滑肌细胞STAT3/NFAT轴，推测其可能改善肺血管重构。本课题1.研究内皮素-1、白介素-6激活肺动脉平滑肌细胞STAT3/NFAT轴导致增殖与凋亡失平衡的作用机制及DHEA干预作用；2.构建 PH-LHF模型，观察DHEA对STAT3/NFAT信号通路及肺血管重构的影响。本研究将阐明PH-LHF发病新机制和治疗新策略。

Pulmonary vascular remodeling is the key pathogenesis in the disease of pulmonary hypertension due to left heart failure (PH-LHF). Endothelin-1 and interleukin-6 have been recognized as precipitating factors in the progression of PH-LHF. The active signal transducers and activators of transcription 3 (STAT3)/ nuclear factor of activated T-cell(NFAT) pathway may be responsible for the imbalance of cell proliferation and apoptosis. Dehydroepiandrosterone (DHEA) inhibits the STAT3/NFAT activation in vascular smooth muscle cell and liver cells. We hypothesize that the involvement of STAT3/NFAT may play important role in the progression of PH-LHF and DHEA reverses pulmonary vascular remodeling through the inhibition of STAT3/NFAT axis. To test this hypothesis, this study will be conducted following aspects: (1) study the effect of endothelin-1 and interleukin-6 on the STAT3/NFAT pathway in pulmonary artery smooth muscle cells (PASMCs) and the intervention of DHEA; (2) investigate the effects and mechanisms of DHEA on the prevention and reservation of pulmonary vascular remodeling in a rat model of PH-LHF. Our study will improve understanding of the potential role of STAT3/NFAT pathway in the pathogenesis of PH-LHF and provide potential therapeutic targeting for PH-LHF.