Zhang Yiwei, Tian Kun, Wang Yan, Zhang Rong, Shang Jiawei, Jiang Wei, Wang Aizhong
Department of Anesthesiology, the Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, China.
Int J Mol Sci. 2016 Jul 21;17(7):1183. doi: 10.3390/ijms17071183.
This study was designed to investigate the role of aquaporin1 (AQP1) in the pathologic process of pulmonary edema induced by fat embolism syndrome (FES) and the effects of a free fatty acid (FFA) mixture on AQP1 expression in pulmonary microvascular endothelial cells (PMVECs). In vivo, edema was more serious in FES mice compared with the control group. The expression of AQP1 and the wet-to-dry lung weight ratio (W/D) in the FES group were significantly increased compared with the control group. At the same time, inhibition of AQP1 decreased the pathological damage resulting from pulmonary edema. Then we performed a study in vitro to investigate whether AQP1 was induced by FFA release in FES. The mRNA and protein level of AQP1 were increased by FFAs in a dose- and time-dependent manner in PMVECs. In addition, the up-regulation of AQP1 was blocked by the inhibitor of p38 kinase, implicating the p38 MAPK pathway as involved in the FFA-induced AQP1 up-regulation in PMVECs. Our results demonstrate that AQP1 may play important roles in pulmonary edema induced by FES and can be regarded as a new therapy target for treatment of pulmonary edema induced by FES.
本研究旨在探讨水通道蛋白1（AQP1）在脂肪栓塞综合征（FES）所致肺水肿病理过程中的作用，以及游离脂肪酸（FFA）混合物对肺微血管内皮细胞（PMVECs）中AQP1表达的影响。在体内，与对照组相比，FES小鼠的水肿更严重。与对照组相比，FES组中AQP1的表达及肺组织干湿重比（W/D）显著增加。同时，抑制AQP1可减轻肺水肿所致的病理损伤。随后我们进行了体外研究，以探讨FES中FFA释放是否诱导AQP1表达。在PMVECs中，FFA以剂量和时间依赖性方式增加AQP1的mRNA和蛋白水平。此外，p38激酶抑制剂可阻断AQP1的上调，提示p38丝裂原活化蛋白激酶（MAPK）通路参与FFA诱导的PMVECs中AQP1上调。我们的结果表明，AQP1可能在FES所致肺水肿中起重要作用，可被视为治疗FES所致肺水肿的新治疗靶点。
