肺静脉闭塞病（PVOD）是一种以肺小静脉弥漫性阻塞为病理特征的静脉性肺动脉高压，病因目前仍不明确，该病极易误诊为特发性肺动脉高压。研究发现EIF2AK4或BMPR2基因发生突变能引起PVOD，可是机理不明确。根据肺动脉高压患者异常的内皮细胞间质转化与BMPR2基因突变相关，即BMPR2基因突变可导致TGFβ表达增加，最终诱发肺血管内皮细胞发生间质转化；前期我们研究发现丝裂霉素(MMC)诱导的PVOD模型大鼠增厚的肺微血管内膜层有大量胶原沉积，内膜层表达间质细胞标记物a-Sma；发现MMC处理体外培养肺静脉内皮细胞TGF-β1以及p-Smad3蛋白表达上升。我们提出PVOD患者肺静脉内皮细胞发生内皮间质转化；MMC通过激活TGFβ/Smad信号通路分子的表达和活性，导致肺静脉内皮细胞发生间质转化的假设。希望藉此研究进一步了解该病发病机制，并对该病的预防、治疗和药物开发提供理论依据。

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary arterial hypertension characterized by the obstruction of small pulmonary veins and a dismal prognosis. It is frequently misclassified as idiopathic pulmonary arterial hypertension (PAH). PVOD may be sporadic or heritable because of biallelic mutation of the EIF2AK4 and BMPR2 gene. As we know, the abnormal endothelial mesenchymal transition (EMT) in pulmonary hypertension (PH) patients had been proved to be closely related with the genic mutation of BMPR2, which could enhance the expression of TGFβ1, and ultimately lead to mesenchymal transition of pulmonary vascular endothelial cells. Additionally, we had found that α-SMA, a mesenchymal cell marker, expressed in the pulmonary vein endothelial of mitomycin (MMC)-induced PVOD rat model, and the expression of TGF-β and p-smad3 protein increased in the MMC-induced pulmonary vein endothelial cells. Based on this, we suppose that EMT happened in the pulmonary vein endothelia cells of PVOD patients, and MMC could activate TGFβ/BMP signaling pathways. We anticipate further understanding the mechanism of PVOD, and help developing new therapeutic approaches for the treatment of this devastating disease.