Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid
Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid
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DOI：
10.1152/ajplung.00300.2011
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发表时间：
2012-07-01
影响因子：
4.9
通讯作者：
Natarajan, Ramesh
中科院分区：
文献类型：
--
作者：
Fisher, Bernard J.;Kraskauskas, Donatas;Natarajan, Ramesh
Fisher BJ、Kraskauskas D、Martin EJ、Farkas D、Wegelin JA、Brophy D、Ward KR、Voelkel NF、Fowler AA 3rd、Natarajan R。抗坏血酸引起的腹部脓毒症急性肺损伤的减弱机制。 Am J Physiol Lung Cell Mol Physiol 303：L20-L32，2012 年。首次发表于 2012 年 4 月 20 日； doi:10.1152/ajplung.00300.2011.-肺部和腹部的细菌感染是败血症的最常见原因之一。腹膜炎常常导致急性肺损伤（ALI）。最近的报告表明，肠外维生素 C [抗坏血酸 (AscA)] 在败血症的发病机制中具有潜在益处。因此，我们研究了在腹部腹膜炎介导的 ALI 情况下补充维生素 C 的机制。我们假设补充维生素 C 可以通过恢复肺泡上皮屏障完整性和预防脓毒症相关凝血病来保护肺部。雄性 C57BL/6 小鼠在接受 AscA (200 mg/kg) 或脱氢抗坏血酸 (200 mg/kg) 前 30 分钟腹腔注射粪便干溶液以诱导腹膜炎 (FIP)。检查的变量包括存活率、ALI程度、肺部炎症标志物（髓过氧化物酶、趋化因子）、支气管肺泡上皮通透性、肺泡液清除率、上皮离子通道和泵表达（水通道蛋白5、囊性纤维化跨膜电导调节剂、上皮钠通道和Na+-K+-ATP酶）、紧密连接蛋白表达（claudins、occludins、封闭带）、脓毒症血液的细胞骨架重排（F-肌动蛋白聚合）和凝血参数（血栓弹力图、促凝剂和抗凝剂、纤溶介质）。 FIP 介导的 ALI 的特点是肺上皮通透性受损、肺泡液清除率降低、肺部炎症和中性粒细胞隔离、凝血异常和死亡率增加。肠外输注维生素 C 通过多种机制保护小鼠免受脓毒症的有害后果，包括减弱促炎反应、增强上皮屏障功能、增加肺泡液清除率以及预防脓毒症相关的凝血异常。肠外维生素 C 可能在脓毒症和脓毒症相关急性肺损伤的治疗中发挥作用。
Fisher BJ, Kraskauskas D, Martin EJ, Farkas D, Wegelin JA, Brophy D, Ward KR, Voelkel NF, Fowler AA 3rd, Natarajan R. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. Am J Physiol Lung Cell Mol Physiol 303: L20-L32, 2012. First published April 20, 2012; doi:10.1152/ajplung.00300.2011.-Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na+-K+-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro-and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.