Role of AQP3 in the Vascular Leakage of Sepsis and the Protective Effect of Ss-31
Role of AQP3 in the Vascular Leakage of Sepsis and the Protective Effect of Ss-31
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AQP3在脓毒症血管渗漏中的作用及Ss-31的保护作用
DOI：
10.1097/fjc.0000000000001050
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发表时间：
2021-08-01
影响因子：
3
通讯作者：
Li, Tao
中科院分区：
文献类型：
--
作者：
Zhang, Jie;Wang, Ping;Li, Tao
水通道蛋白（AQP）是一组与水渗透性相关的膜蛋白。研究表明，AQP 在多种疾病中发挥着至关重要的作用。 AQPs是否参与脓毒症后血管通透性调节以及AQPs亚型是否相关尚不清楚。 Ss-31作为一种新型抗氧化剂，对多种疾病具有保护作用。然而，Ss-31是否对脓毒症肺血管通透性具有保护作用以及其作用是否与AQP相关尚不清楚。利用盲肠结扎穿孔诱导的脓毒症大鼠和LPS处理的肺静脉内皮细胞，研究AQPs在肺血管通透性调节中的作用及其与Ss-31的关系。结果显示脓毒症后肺血管通透性明显增加,同时AQP3、4、12表达增加。其中，AQP3与肺血管通透性密切相关。 AQP3的抑制可拮抗单层肺静脉内皮细胞通透性的增加。进一步研究表明脓毒症后caveolin-1（Cav-1）表达增加，occludin表达减少。脓毒症时AQP3的抑制可拮抗Cav-1的减少和occludin的增加。抗氧化剂 Ss-31 降低了 AQP3 的表达和 ROS 水平。同时，Ss-31改善了脓毒症大鼠的肺血管通透性并延长了生存期。总之，AQP3参与脓毒症后肺血管通透性的调节，抗氧化剂Ss-31通过下调AQP3的表达、抑制ROS的产生对肺血管通透性具有保护作用。
Aquaporins (AQPs) are a group of membrane proteins related to water permeability. Studies have shown that AQPs play a vital role in various diseases. Whether AQPs participate in regulating vascular permeability after sepsis and whether the subtype of AQPs is related are unknown. Ss-31, as a new antioxidant, had protective effects on a variety of diseases. However, whether Ss-31 has a protective effect on pulmonary vascular permeability in sepsis and whether its effect is related to AQPs are unclear. Using the cecum ligation perforation-induced septic rat and LPS-treated pulmonary vein endothelial cells, the role of AQPs in the regulation of the permeability of pulmonary vascular and its relationship to Ss-31 were studied. The results showed that the pulmonary vascular permeability significantly increased after sepsis, meanwhile the expressions of AQP3, 4, and 12 increased. Among those, the AQP3 was closely correlated with pulmonary vascular permeability. The inhibition of AQP3 antagonized the increase of the permeability of monolayer pulmonary vein endothelial cells. Further study showed that the expression of caveolin-1 (Cav-1) increased and occludin decreased after sepsis. The inhibition of AQP3 antagonized the decrease of Cav-1 and the increase of occludin in sepsis. Antioxidant Ss-31 decreased the expression of AQP3 and ROS levels. At the same time, Ss-31 improved pulmonary vascular permeability and prolonged survival of sepsis rats. In conclusion, AQP3 participates in the regulation of pulmonary vascular permeability after sepsis, and the antioxidant Ss-31 has a protective effect on pulmonary vascular permeability by downregulating the expression of AQP3 and inhibiting ROS production.