高氧富氢液对急性肺损伤治疗作用及相关临床基础研究

Acute lung injury (ALI) is a common acute and critical disease in clinic with high mortality rates (50-70%), which resulted from uncontrollable inflammation and unimprovable refractory hypoxemia. Recent studies found that the hydrogen could scavenging oxygen free radicals (OR) selectively and regulate early inflammatory response initiated by OR. The hyperoxygenated solution supplied through non-respiratory tract was proved one of the most effective ways to alleviate the hypoxemia in ALI in decades..The hyperoxygenated hydrogen rich solution used in the study was made with microbubble rapid replace and mixed hydrogen-oxygen dissolve technology, which is our independent intellectual property right. The solution, which contained 25.6±2.3mg/L dissolved oxygen and 0.85±0.16mmol/L dissolved hydrogen was injected intravenously or intraperitoneally to evaluate the effect on ALI caused by lipopolysaccharide in rabbits. The study analysed protein, lipid, DNA, free radical, antioxidant capacity, inflammatory factors and NF - κB, AP - 1 to indicate the main effect of LPS/ROS (• OH) /••• / NF - κB (AP - 1) signaling pathways. The study was expecting to illustrate that the hydrogen and oxygen would have synergistic or additive effect pharmacologically, which will provide the theoretical foundation for development and utilization of hyperoxygenated hydrogen rich solution.

急性肺损伤（ALI）是临床常见危重急症，死亡率高达50-70%，其根本原因是失控性炎症反应和顽固性低氧血症难以控制和改善。近年来研究发现氢能选择性清除强活性自由基（OR）,可及时调控OR启动的早期炎症反应。十多年来，使用高氧液通过非呼吸道辅助供氧已通过大样本临床验证，结果说明这是目前缓解严重ALI肺弥散功能障碍性缺氧最有效途径之一。本课题率先应用具有自主知识产权的微泡快速置换折混式溶氢溶氧技术，制备溶解氧为25.6±2.3mg/L和氢为0.85±0.16mmol/L的高氧富氢液，通过静脉或腹腔注射评价对家兔LPS性ALI治疗效果，并以蛋白质、脂质、DNA、自由基、抗氧化能力、炎性因子及和NF-κB、AP-1基因敲除水平为分析指标，揭示LPS/ROS（•OH）/•••/NF-κB(AP-1)为主体的关键信号通路，有望氢氧联合载体能发挥协同或相加的药理作用，为高氧富氢液开发和利用提供理论依据。

急性肺损伤是一种临床上的常见急症其死亡率为50-70%。根本原因是顽固性炎症反应和低氧血症，很难控制和改善。我们建立了腹腔注射脂多糖诱导的急性肺损伤模型，并通过病理切片、炎症因子、干湿比、支气管肺泡灌洗液、免疫组化、电镜、免疫印迹和其他方法评价了肺组织和线粒体的损伤程度。.结论：.1.高氧富氢生理盐水能较好地缓解呼吸功能；.2.高氧富氢生理盐水可改善脂多糖诱导小鼠的肺组织病理学改变和肺部炎症细胞因子；.3.富氢液对脂多糖致小鼠肺部炎症通路的影响；.4.三种生理盐水均能有效抑制细胞凋亡；.5.高氧富氢生理盐水能有效地减少线粒体肿胀、脊线断裂和消失，减少板层体；.6.高氧富氢盐对脂多糖小鼠肺线粒体有保护作用，并影响其线粒体复合物I蛋白的表达；.7.高氧富氢生理盐水可提高肺组织抗氧化活性，降低SOD1和SOD2的表达；.8.富氢生理盐水可降低血清炎症因子，增加中性粒细胞数量，而高氧富氢生理盐水可显著改变脂多糖诱导的血小板减少。. 我们目前的研究发现，高氧富氢盐可通过改善线粒体功能障碍来预防脂多糖诱导的急性肺损伤，从而减轻氧化应激和炎症反应。我们发现富氢盐水和高氧盐水的联合作用优于它们各自的保护作用，针对缺氧损伤两者的具体分子机制不同，氧在改善机体缺氧方面有着非常好的作用，而氢在炎症和抗凋亡机制中起着更重要的作用。.本研究为氢气和氧气的临床干预提供了新的思路和实验依据。