Background Recent research suggests that β2-adrenergic agonists increase alveolar fluid clearance （AFC） under physiologic and pathologic conditions. It is unknown whether β3-adrenergic agonists also increase AFC u...Background Recent research suggests that β2-adrenergic agonists increase alveolar fluid clearance （AFC） under physiologic and pathologic conditions. It is unknown whether β3-adrenergic agonists also increase AFC under pathologic conditions. The aim of this study was to investigate the effect of β3-adrenergic agonists on AFC following hypoxic lung injury and the mechanisms involved. Methods Hypoxic rats were exposed to 10% oxygen. BRL-37344 （133-adrenergic agonist） or CGP-12177 （selective β3-adrenergic agonist） alone or combined with β receptor antagonists, sodium channel blockers, or Na＋/＋^-ATPase blockers were perfused into the alveolar space of rats exposed to 10% oxygen for 48 hours. Total lung water content （TLW） and AFC were measured. Results AFC did not change for the first 24 hours but then decreased after 48-hour exposure to 10% oxygen. The perfusion of BRL-37344 or CGP-12177 significantly increased AFC in normal and hypoxic rats. The AFC-stimulating effect of CGP-12177 was lowered with amiloride （a Na＋ channel blocker） and ouabain （a Na~/K^-ATPase inhibitor） by 37% and 49%, respectively. Colchicine significantly inhibited the effect of CGP-12177. Conclusions These findings suggest that β3-adrenergic agonists can increase AFC during hypoxic lung injury in rats and accelerate the amelioration of pulmonary edema.展开更多
Objective：Acute respiratory distress syndrome （ARDS） is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impede...Objective：Acute respiratory distress syndrome （ARDS） is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance （AFC） in ARDS.Data Sources：Articles published up to September 2017 were selected from the PubMed, with the keywords of ＂alveolar fluid clearance＂ or ＂lung edema＂ or ＂acute lung injury＂ or ＂acute respiratory distress syndrome＂ , and ＂specialized pro-resolving mediators＂ or ＂lipoxin＂ or ＂resolvin＂ or ＂protectin＂ or ＂maresin＂ or ＂alveolar epithelial cells＂ or ＂aspirin-triggered lipid mediators＂ or ＂carbon monoxide and heme oxygenase＂ or ＂annexin A1＂ .Study Selection：We included all relevant articles published up to September 2017, with no limitation of study design.Results：Specialized pro-resolving mediators （SPMs）, as the proinflammatory mediators, not only upregulated epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator （CFTR）, and aquaporins levels, but also improved Na,K-ATPase activity to promote AFC in ARDS. In addition to the direct effects on ion channels and pumps of the alveolar epithelium, the SPMs also inhibited the inflammatory cytokine expression and improved the alveolar epithelial cell repair to enhance the AFC in ARDS.Conclusions：The present review discusses a novel mechanism for pulmonary edema fluid reabsorption. SPMs might provide new opportunities to design ＂reabsorption-targeted＂ therapies with high degrees of precision in controlling ALI/ARDS.展开更多
目的布比卡因是长效酰胺类局麻药,本研究旨在观察布比卡因对人肺上皮细胞短路电流的影响,并探讨可能的机制。方法应用尤斯灌流室装置测定H441单层细胞的短路电流。由总电流减去阿米洛利抑制后的电流算得阿米洛利敏感性电流,以用药前H44...目的布比卡因是长效酰胺类局麻药,本研究旨在观察布比卡因对人肺上皮细胞短路电流的影响,并探讨可能的机制。方法应用尤斯灌流室装置测定H441单层细胞的短路电流。由总电流减去阿米洛利抑制后的电流算得阿米洛利敏感性电流,以用药前H441单层细胞的阿米洛利敏感性电流初始值为100%对照。用100μmol·L^(-1)布比卡因处理H441细胞,在0、15、30、60 min 4个时间点提取蛋白用于Western blot,研究布比卡因对ERK1/2蛋白磷酸化的影响。结果布比卡因能够剂量依赖性抑制H441单层细胞的短路电流,此电流可被阿米洛利抑制;Western blot结果显示,布比卡因能够促进ERK1/2蛋白磷酸化。结论布比卡因通过抑制人肺上皮细胞阿米洛利敏感性电流而降低肺泡上皮离子转运,其机制可能与其促进ERK1/2蛋白磷酸化有关。临床上对伴有肺部疾患的病人应用布比卡因时应考虑其可能对肺泡上皮液体清除的影响。展开更多
目的探讨精氨酸抗利尿激素(AVP)对急性肺损伤肺水肿液清除作用。方法 48只健康成年的雄性SD大鼠随机分为对照组、模型组(ALI组)、AVP组,观察各组肺组织病理形态学、肺水含量、肺泡上皮通透性及肺泡液体清除率(AFC)变化,测定肺泡上皮钠通...目的探讨精氨酸抗利尿激素(AVP)对急性肺损伤肺水肿液清除作用。方法 48只健康成年的雄性SD大鼠随机分为对照组、模型组(ALI组)、AVP组,观察各组肺组织病理形态学、肺水含量、肺泡上皮通透性及肺泡液体清除率(AFC)变化,测定肺泡上皮钠通道(ENa C)和钠/钾ATP酶(Na+,K+-ATPase)表达情况。结果经AVP治疗后,模型组肺泡上皮通透性(0.27±0.15 vs0.59±0.19)及肺水含量(5.01±1.59 vs 8.67±1.79)减轻,AFC增加(23.56±4.51 vs 8.28±3.57),α-ENa C(1.296±0.322 vs 0.349±0.141)和α1-Na+,K+-ATPase表达增加(1.421±0.389 vs 0.338±0.186),均有显著差异(P<0.05)。结论 AVP能促进AFC,其作用途径可能是上调α-ENa C和α1-Na+,K+-ATPase通道蛋白实现的。展开更多
文摘Background Recent research suggests that β2-adrenergic agonists increase alveolar fluid clearance （AFC） under physiologic and pathologic conditions. It is unknown whether β3-adrenergic agonists also increase AFC under pathologic conditions. The aim of this study was to investigate the effect of β3-adrenergic agonists on AFC following hypoxic lung injury and the mechanisms involved. Methods Hypoxic rats were exposed to 10% oxygen. BRL-37344 （133-adrenergic agonist） or CGP-12177 （selective β3-adrenergic agonist） alone or combined with β receptor antagonists, sodium channel blockers, or Na＋/＋^-ATPase blockers were perfused into the alveolar space of rats exposed to 10% oxygen for 48 hours. Total lung water content （TLW） and AFC were measured. Results AFC did not change for the first 24 hours but then decreased after 48-hour exposure to 10% oxygen. The perfusion of BRL-37344 or CGP-12177 significantly increased AFC in normal and hypoxic rats. The AFC-stimulating effect of CGP-12177 was lowered with amiloride （a Na＋ channel blocker） and ouabain （a Na~/K^-ATPase inhibitor） by 37% and 49%, respectively. Colchicine significantly inhibited the effect of CGP-12177. Conclusions These findings suggest that β3-adrenergic agonists can increase AFC during hypoxic lung injury in rats and accelerate the amelioration of pulmonary edema.
文摘Objective：Acute respiratory distress syndrome （ARDS） is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance （AFC） in ARDS.Data Sources：Articles published up to September 2017 were selected from the PubMed, with the keywords of ＂alveolar fluid clearance＂ or ＂lung edema＂ or ＂acute lung injury＂ or ＂acute respiratory distress syndrome＂ , and ＂specialized pro-resolving mediators＂ or ＂lipoxin＂ or ＂resolvin＂ or ＂protectin＂ or ＂maresin＂ or ＂alveolar epithelial cells＂ or ＂aspirin-triggered lipid mediators＂ or ＂carbon monoxide and heme oxygenase＂ or ＂annexin A1＂ .Study Selection：We included all relevant articles published up to September 2017, with no limitation of study design.Results：Specialized pro-resolving mediators （SPMs）, as the proinflammatory mediators, not only upregulated epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator （CFTR）, and aquaporins levels, but also improved Na,K-ATPase activity to promote AFC in ARDS. In addition to the direct effects on ion channels and pumps of the alveolar epithelium, the SPMs also inhibited the inflammatory cytokine expression and improved the alveolar epithelial cell repair to enhance the AFC in ARDS.Conclusions：The present review discusses a novel mechanism for pulmonary edema fluid reabsorption. SPMs might provide new opportunities to design ＂reabsorption-targeted＂ therapies with high degrees of precision in controlling ALI/ARDS.
文摘目的布比卡因是长效酰胺类局麻药,本研究旨在观察布比卡因对人肺上皮细胞短路电流的影响,并探讨可能的机制。方法应用尤斯灌流室装置测定H441单层细胞的短路电流。由总电流减去阿米洛利抑制后的电流算得阿米洛利敏感性电流,以用药前H441单层细胞的阿米洛利敏感性电流初始值为100%对照。用100μmol·L^(-1)布比卡因处理H441细胞,在0、15、30、60 min 4个时间点提取蛋白用于Western blot,研究布比卡因对ERK1/2蛋白磷酸化的影响。结果布比卡因能够剂量依赖性抑制H441单层细胞的短路电流,此电流可被阿米洛利抑制;Western blot结果显示,布比卡因能够促进ERK1/2蛋白磷酸化。结论布比卡因通过抑制人肺上皮细胞阿米洛利敏感性电流而降低肺泡上皮离子转运,其机制可能与其促进ERK1/2蛋白磷酸化有关。临床上对伴有肺部疾患的病人应用布比卡因时应考虑其可能对肺泡上皮液体清除的影响。
文摘目的探讨精氨酸抗利尿激素(AVP)对急性肺损伤肺水肿液清除作用。方法 48只健康成年的雄性SD大鼠随机分为对照组、模型组(ALI组)、AVP组,观察各组肺组织病理形态学、肺水含量、肺泡上皮通透性及肺泡液体清除率(AFC)变化,测定肺泡上皮钠通道(ENa C)和钠/钾ATP酶(Na+,K+-ATPase)表达情况。结果经AVP治疗后,模型组肺泡上皮通透性(0.27±0.15 vs0.59±0.19)及肺水含量(5.01±1.59 vs 8.67±1.79)减轻,AFC增加(23.56±4.51 vs 8.28±3.57),α-ENa C(1.296±0.322 vs 0.349±0.141)和α1-Na+,K+-ATPase表达增加(1.421±0.389 vs 0.338±0.186),均有显著差异(P<0.05)。结论 AVP能促进AFC,其作用途径可能是上调α-ENa C和α1-Na+,K+-ATPase通道蛋白实现的。
