Lipoxin A4 Activates Alveolar Epithelial Sodium Channel, Na, K-ATPase, and Increases Alveolar Fluid Clearance
Lipoxin A4 Activates Alveolar Epithelial Sodium Channel, Na, K-ATPase, and Increases Alveolar Fluid Clearance
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DOI：
10.1165/rcmb.2012-0274oc
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发表时间：
2013-05-01
影响因子：
6.4
通讯作者：
Jin, Sheng-Wei
中科院分区：
文献类型：
--
作者：
Wang, Qian;Lian, Qing-Quan;Jin, Sheng-Wei
肺泡上皮钠通道(ENaC)和Na，K-ATPase在肺水肿的消退中起关键作用。用伊文思蓝标记的白蛋白示踪剂(5ml/kg)滴入5%等渗牛血清白蛋白溶液，测定肺泡液体清除率(AFC)，并测定伊文思蓝标记的白蛋白浓度随时间的变化。脂氧素A(4)和脂氧素受体激动剂(5(S)，6(R)-7-三羟甲基17庚酸酯)可显著刺激油酸(OA)所致肺损伤的AFC，减轻肺水肿。脂氧素A4和5(S)，6(R)-7-三羟甲基17-庚酸酯不仅上调肺组织ENaCα和ENaCγ亚基蛋白表达，而且增加Na，K-ATPaseα1亚基蛋白表达和Na，K-ATPase活性。脂氧素A4治疗组与OA组细胞内cAMP水平差异无统计学意义。脂氧素A4处理后，细胞内cGMP水平显著降低。脂氧素A4受体拮抗剂丁氧羰基-Phe-Leu-Phe-Leu-Ph(脂氧素A4受体拮抗剂)可阻断脂氧素A4对OA肺损伤的保护作用。脂氧素A(4)可增加脂多糖刺激的原代大鼠肺泡II型上皮细胞ENaCα和ENaCγ亚基蛋白表达及Na，K-ATPase活性。脂氧素A(4)通过激活肺泡上皮ENaC和Na，K-ATPase刺激AFC。
Edema fluid resorption is critical for gas exchange, and both alveolar epithelial sodium channel (ENaC) and Na,K-ATPase are accredited with key roles in the resolution of pulmonary edema. Alveolar fluid clearance (AFC) was measured in in situ ventilated lungs by instilling isosmolar 5% BSA solution with Evans Blue-labeled albumin tracer (5 ml/kg) and measuring the change in Evans Blue-labeled albumin concentration over time. Treatment with lipoxin A(4) and lipoxin receptor agonist (5(S), 6(R)-7-trihydroxymethyl 17 heptanoate) significantly stimulated AFC in oleic acid (OA)-induced lung injury, with the outcome of decreased pulmonary edema. Lipoxin A4 and 5(S), 6(R)-7-trihydroxymethyl 17 heptanoate not only up-regulated the ENaC alpha and ENaC gamma subunits protein expression, but also increased Na,K-ATPase alpha 1 subunit protein expression and Na,K-ATPase activity in lung tissues. There was no significant difference of intracellular cAMP level between the lipoxin A4 treatment and OA group. However, the intracellular cGMP level was significantly decreased after lipoxin A4 treatment. The beneficial effects of lipoxin A4 were abrogated by butoxycarbonyl-Phe-Leu-Phe-Leu-Ph (lipoxin A4 receptor antagonist) in OA-induced lung injury. In primary rat alveolar type II epithelial cells stimulated with LPS, lipoxin A(4) increased ENaC alpha and ENaC gamma subunits protein expression and Na,K-ATPase activity. Lipoxin A(4) stimulated AFC through activation of alveolar epithelial ENaC and Na,K-ATPase.