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氢气和一氧化氮联合治疗急性肺损伤

已有 4605 次阅读 2015-2-3 20:57 |个人分类:呼吸氢气|系统分类:科研笔记|关键词:学者

氢气不仅能中和强毒性羟基自由基,也能中和亚硝酸阴离子,亚硝酸阴离子是一氧化氮和超氧阴离子反应产生。一氧化氮对肺损伤也具有治疗作用,在治疗的同时,会因为一氧化氮和肺组织中的超氧阴离子反应产生亚硝酸阴离子带来危害。如果联合使用一氧化氮和氢气,则不仅可以发挥两者对氧化损伤和肺损伤的治疗作用,而且可以减少一氧化氮治疗导致的亚硝酸阴离子增加,应该是一种比较理想的治疗策略。

最近,中国天津医科大学麻醉学研究小组,在《休克》杂志上发表最新研究论文,证明联合呼吸一氧化氮和氢气能有效治疗急性肺损伤。

Acute lung injury (ALI)is still a leading cause of morbidity and mortality in critically ill patients.Inhaled nitric oxide (NO) has been reported to ameliorate ALI. However,reactive nitrogen species (RNS) produced by NO can cause lung injury. Since hydrogengas (H2) is reported to eliminate peroxynitrite, it is expected to reduce theadverse effects of NO. Moreover, we have found that H2 inhalation can attenuatelung injury. Therefore, we hypothesized that combination therapy with NO and H2might afford more potent therapeutic strategies for ALI. In the present study,a mouse model of ALI was induced by intratracheal administration oflipopolysaccharide (LPS). The animals were treated with inhaled NO (20 ppm), H2(2%), or NO+H2, starting 5 min after LPS administration for 3 hours. We foundthat LPS-challenged mice exhibited significant lung injury characterized by thedeterioration of histopathology and histologic scores, wet-to-dry weight ratio,oxygenation index (PaO2/FiO2) as well as total protein in the bronchoalveolarlavage fluid (BALF), which was attenuated by NO or H2 treatment alone.Combination therapy with NO and H2 had a more beneficial effect withsignificant interaction between the two. While the nitrotyrosine level in lungtissue was prominent after NO inhalation alone, it was significantly eliminatedafter breathing a mixture of NO with H2. Furthermore, NO or H2 treatment alonemarkedly attenuated LPS-induced lung neutrophils recruitment and inflammation,as evidenced by down-regulation of lung myeloperoxidase activity, total cellsand polymorphonuclear neutrophils in BALF, as well as pro-inflammatorycytokines (TNF-α, IL-1β, IL-6 and HMGB1) and chemokines (KC, MIP-1α, MIP-2, andMCP-1) in BALF. Combination therapy with NO and H2 had a more beneficial effectagainst lung inflammatory response. Moreover, combination therapy with NO andH2 could more effectively inhibit LPS-induced pulmonary early and late NF-κBactivation as well as pulmonary cell apoptosis. In addition, combinationtreatment with inhaled NO and H2 could also significantly improve the lunginjury in polymicrobial sepsis. Combination therapy with sub-thresholdconcentrations of NO and H2 still had a significantly beneficial effect againstlung injury induced by LPS and polymicrobial sepsis. Collectively, theseresults demonstrate that combination therapy with NO and H2 provides enhancedtherapeutic efficacy for ALI.




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