Anti-inflammatory treatment strategies for ischemia/reperfusion injury in transplantation.
Anti-inflammatory treatment strategies for ischemia/reperfusion injury in transplantation.
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DOI：
10.1186/1476-9255-7-27
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发表时间：
2010-05-28
期刊：
影响因子：
--
通讯作者：
Heemann U
中科院分区：
文献类型：
--
作者：
Lutz J;Thürmel K;Heemann U
移植物中的炎症反应对移植物的急性和长期功能都有重要影响。移植物组织炎症反应的主要原因是排斥反应、感染以及缺血/再灌注损伤。后者特别令人感兴趣，因为它影响到移植过程中的每一个实体器官。I/R损伤损害了移植肾的急性和长期功能，并与急性排斥反应增加有关，这再次影响了移植肾的长期预后。I/R损伤是在长时间低氧条件下ATP耗竭的结果。进一步的组织损伤是由于缺血损伤后组织的再灌注造成的。适应性细胞反应激活先天免疫系统及其Toll样受体和补体系统以及适应性免疫系统。这会导致严重的炎症组织反应，免疫细胞渗透到组织中。损伤是由各种细胞因子、趋化因子、黏附分子和细胞外基质化合物介导的。这些因子的表达受特定转录因子的调节，其中NF-κB是炎症的关键调节因子之一。预防或治疗I/R损伤的策略包括阻断细胞因子/趋化因子、黏附分子、核因子-κB、特异性MAPK、金属蛋白酶、诱导保护性基因和调节先天免疫系统。此外，捐赠者的预适应是一个密集的研究领域。在这里，我们分析了药物治疗以及传统冷藏溶液中的新添加剂，以及移植物灌流的新技术，或避免冷损伤和移植物缺血的常温保存方法。然而，与近年来在I/R损伤领域积累的大量实验知识相比，I/R损伤领域的临床试验数量有限。I/R损伤治疗的未来活动应侧重于将实验方案转化为临床试验，以减少I/R损伤，从而改善移植物的短期和长期结果。
Inflammatory reactions in the graft have a pivotal influence on acute as well as long-term graft function. The main reasons for an inflammatory reaction of the graft tissue are rejection episodes, infections as well as ischemia/reperfusion (I/R) injury. The latter is of particular interest as it affects every solid organ during the process of transplantation. I/R injury impairs acute as well as long-term graft function and is associated with an increased number of acute rejection episodes that again affect long-term graft outcome. I/R injury is the result of ATP depletion during prolonged hypoxia. Further tissue damage results from the reperfusion of the tissue after the ischemic insult. Adaptive cellular responses activate the innate immune system with its Toll-like receptors and the complement system as well as the adaptive immune system. This results in a profound inflammatory tissue reaction with immune cells infiltrating the tissue. The damage is mediated by various cytokines, chemokines, adhesion molecules, and compounds of the extracellular matrix. The expression of these factors is regulated by specific transcription factors with NF-κB being one of the key modulators of inflammation. Strategies to prevent or treat I/R injury include blockade of cytokines/chemokines, adhesion molecules, NF-κB, specific MAP kinases, metalloproteinases, induction of protective genes, and modulation of the innate immune system. Furthermore, preconditioning of the donor is an area of intense research. Here pharmacological treatment as well as new additives to conventional cold storage solutions have been analyzed together with new techniques for the perfusion of grafts, or methods of normothermic storage that would avoid the problem of cold damage and graft ischemia. However, the number of clinical trials in the field of I/R injury is limited as compared to the large body of experimental knowledge that accumulated during recent years in the field of I/R injury. Future activities in the treatment of I/R injury should focus on the translation of experimental protocols into clinical trials in order to reduce I/R injury and, thus, improve short- as well as long-term graft outcome.
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影响因子：
13.5
作者：
Huet, PM;Nagaoka, MR;Bilodeau, M
通讯作者：
Bilodeau, M
影响因子：
19.6
作者：
Hauet, T;Goujon, JM;Vandewalle, A
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影响因子：
4.1
作者：
Evans, PC;Ovaa, H;Smith, TS
通讯作者：
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影响因子：
30.5
作者：
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通讯作者：
Ma, A
DOI：
10.1097/01.asn.0000050760.87113.25
发表时间：
2003-03-01
影响因子：
13.6
作者：
Blydt-Hansen, TD;Katori, M;Buelow, R
通讯作者：
Buelow, R