Acute respiratory distress syndrome (ARDS) is a lethal clinical syndrome characterized by damage of the epithelial barriers and accumulation of pulmonary edema fluid. Protectin conjugates in tissue regeneration 1 (PCTR1), an endogenously produced lipid mediator, are believed to exert anti-inflammatory and pro-resolution effects. PCTR1 (1 µg/kg) was injected at 8 hr after lipopolysaccharide (LPS; 14 mg/kg) administration, and the rate of pulmonary fluid clearance was measured in live rats at 1 hr after PCTR1 treatment. The primary type II alveolar epithelial cells were cultured with PCTR1 (10 nmol/ml) and LPS (1 μg/ml) for 8 hr. PCTR1 effectively improved pulmonary fluid clearance and ameliorated morphological damage and reduced inflammation of lung tissue, as well as improved the survival rate in the LPS-induced acute lung injury (ALI) model. Moreover, PCTR1 markedly increased sodium channel expression as well as Na, K-ATPase expression and activity in vivo and in vitro. In addition, PCTR1i also upregulated the expression of LYVE-1 in vivo. Besides that, BOC-2, HK7, and LY294002 blocked the promoted effect of PCTR1 on pulmonary fluid clearance. Taken together, PCTR1 upregulates sodium channels' expression via activating the ALX/cAMP/P-Akt/Nedd4-2 pathway and increases Na, K-ATPase expression and activity to promote alveolar fluid clearance. Moreover, PCTR1 also promotes the expression of LYVE-1 to recover the lymphatic drainage resulting in the increase of lung interstitial fluid clearance. In summary, these results highlight a novel systematic mechanism for PCTR1 in pulmonary edema fluid clearance after ALI/ARDS, suggesting its potential role in a therapeutic approach for ALI/ARDS.

译文

急性呼吸窘迫综合征 (ARDS) 是一种致命的临床综合征,其特征是上皮屏障受损和肺水肿液积聚。组织再生1 (PCTR1) 中的保护素缀合物 (一种内源性产生的脂质介质) 被认为具有抗炎和促分辨作用。在脂多糖 (LPS; 14  mg/kg) 给药后8 hr小时注射PCTR1 (1  μ g/kg),并在PCTR1处理后1  小时测量活大鼠的肺液清除率。原代II型肺泡上皮细胞用PCTR1 (10  nmol/ml) 和LPS (1  μ g/ml) 培养8  小时。在LPS诱导的急性肺损伤 (ALI) 模型中,PCTR1有效地改善了肺液体清除率,改善了形态损伤,减轻了肺组织的炎症反应,并提高了生存率。此外,PCTR1在体内和体外显着增加了钠通道的表达以及Na,K-ATPase的表达和活性。此外,PCTR1i还上调了LYVE-1在体内的表达。此外,BOC-2,HK7和LY294002阻断了PCTR1对肺液清除的促进作用。合在一起,PCTR1通过激活ALX/cAMP/P-Akt/Nedd4-2途径上调钠通道的表达,并增加Na,K-ATPase的表达和活性以促进肺泡液清除。此外,PCTR1还促进LYVE-1的表达以恢复淋巴引流,导致肺间质液清除率增加。总之,这些结果强调了PCTR1在ALI/ARDS后肺水肿液体清除中的一种新的系统机制,表明其在ALI/ARDS治疗方法中的潜在作用。

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