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氙气在常压下就可以产生明显的麻醉作用,大量研究表明,呼吸氙气对许多器官缺血再灌注损伤等典型器官损伤具有明显保护作用。英国帝国大学麻醉学马大青教授是氙气效应研究领域有非常多的贡献。2009年本人曾有幸和马教授共同被中国青年麻醉医师学会年会邀请,分别作大会特邀发言,本人介绍的是氢气生物效应研究,马教授介绍的就是氙气生物血效应研究。
最近马教授和国内第三军医大学合作,开展了氙气溶解的新型器官保护液对肾脏体外冷缺血的保护效应研究。该研究发现,体外监测肾脏受保护的形态学研究,BCL-2、热休克蛋白70。将受到该溶液处理的肾脏移植后,移植后肾脏功能明显改善,组织学研究发现肾脏炎症细胞浸润和纤维化改变均受到明显抑制。采用人肾脏细胞的研究表明,氙气对细胞保护存在类似变化,通过RNA干扰技术证明热休克蛋白70表达上调受到阻断后上述效应消失。该研究首次证明体外氙气溶解可以作为新型器官保护液,由于氙气具有很大的生物安全性,这种方法具有明显的应用前景。该文章发表在The FASEB Journal。研究方法和设计值得学习和借鉴,建议仔细阅读。
*Department of Surgery and Cancer, Section of Anaesthetics, Pain Medicine, and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK;
Renal transplantation remains the best treatment option for patients with end-stage renal failure. However, the shortage of renalgrafts remains a big challenge. Renal graft ischemic injuries that occur before and after graft retrieval have a devastating effect on graft survival, especially on grafts from marginal donors. This study was conducted to assess the protective effect against ischemic injury of a preservative solution supplemented with xenon (Xe), when used on exvivo kidney grafts in a rat renal transplant model, and to explore the underlying mechanisms in vitro. Lewis rat renalgrafts were stored in Soltran preservative solution at 4°C, saturated with nitrogen (N2) or Xe gas (70% Xe or N2, with 5% CO2 balanced with O2) for 24 or 48 h. Grafts stored in Xe-saturated preservative solution demonstrated significantly less severe histopathologic changes, together with enhanced B-cell lymphoma (Bcl)-2 and heat shock protein (HSP)-70 expression. After engraftment in the Lewis rat recipient, renal function was significantly improved in the Xe-treated grafts, and macrophage infiltration and fibrosis were reduced. Xe exposure enhanced Bcl-2 and HSP-70 expression in human renal tubular epithelial (HK-2) cells and prevented mitochondrial and nuclear damage. The release of the apoptogenic factors cytochrome c, apoptosis-inducing factor (AIF), and proinflammatory high-mobility group protein B1 (HMGB-1) was effectively suppressed. This study thus demonstrated for the first time that Xe confers renoprotection on renalgraftsexvivo and is likely to stabilize cellular structure during ischemic insult. The current study has significant clinical implications, in which the use of Xe exvivo could enhance the marginaldonorpool of renalgrafts by preventing graft loss due to ischemia.-Zhao, H., Ning, J., Savage, S., Kang, H., Lu, K., Zheng, X., George, A. J. T., Ma D. A novelstrategy for preservingrenalgrafts in an exvivosetting: potential for enhancing the marginaldonorpool.
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