前B细胞克隆增强因子抑制肺上皮细胞钠水转运系统清除体外循环术后肺水肿液的机制研究

Pulmonary edema is part of the results after cardiopulmonary bypass，and it is mainly related to the increase of pulmonary micro vascular permeability and the reduction of alveolar fluid clearance. Sodium and water transportation system（ENaC、NKA and AQP) are the primary engine of alveolar fluid clearance. We have found out that PBEF increase the permeability of pulmonary endothelial cells through MAPKs. PBEF affect the expression of sodium and water transport system. However, PBEF inhibit sodium and water transport system on the alveolar fluid clearance is still to be explored. So we propose in the hypothesis that PBEF may through the MAPKs signal pathway inhibit sodium and water transport system on alveolar fluid clearance.To test this hypothesis, we will explore via hypoxia and oxygen recovery model of lung epithelial cells and deep hypothermia circulatory arrest in rats model. 1、PBEF expression change affects the lung epithelial sodium and water transport system.2、PBEF suppress sodium and water transportation system on alveolar fluid clearance through P38MAPK? Or ERK1/2? Or PI3K-Akt?3、PBEF reduce the expression of ENaC? Or NKA? Or AQP? It would serve as a new theoretical basis of protecting lung injury after CPB.

肺泡毛细血管通透性增加和肺泡内液体清除减少是体外循环术后肺水肿的重要原因,钠水转运系统（ENaC、NKA和AQP)是清除肺水肿液的主要动力。我们前期研究发现前B细胞克隆增强因子(PBEF)可通过MAPK家族信号通路增加肺内皮细胞通透性，且PBEF也影响了钠水转运系统的表达，但PBEF抑制肺上皮细胞钠水转运系统清除肺水肿液的具体机制知之甚少，据此，我们提出假说：PBEF可能通过MAPK家族信号通路抑制钠水转运系统清除肺水肿液，为验证这一假说：本项目采用肺上皮细胞缺氧复氧模型和大鼠深低温停循环模型，从细胞和动物水平探讨：1、PBEF表达变化对肺上皮细胞钠水转运系统的影响。2、PBEF通过P38MAPK、ERK1/2、PI3K-Akt中哪些通路抑制钠水转运系统清除肺水肿液。3、PBEF降低钠水转运系统中ENaC、NKA和AQP的哪种或哪几种的表达，为体外循环术后肺保护提供新的理论基础。

急性肺损伤是体外循环（cardiopulmonary bypass,CPB）术后最常见的并发症之一，前B细胞克隆增强因子（PBEF）作为一种在细胞内广泛表达的酶，其表达变化与肺泡毛细血管通透性增加和肺泡内液体清除减少有关。本研究采用肺上皮细胞缺氧复氧模型和大鼠深低温停循环模型，从细胞和动物水平讨论PBEF调控钠水转运系统的机制，结果发现从细胞和动物水平PBEF抑制ENaC、NKA和AQP1的表达，并通过MAPK、ERK1/2、Akt的磷酸化共同调控钠水转运系统相关因子的表达。这些研究结果提示：可通过干扰PBEF为体外循环术后肺保护提供新的方向。