IMMUNE STATUS AND APOPTOSIS ACTIVATION DURING BRAIN DEATH
IMMUNE STATUS AND APOPTOSIS ACTIVATION DURING BRAIN DEATH
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DOI：
10.1097/shk.0b013e3181b65b99
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发表时间：
2010-04-01
期刊：
影响因子：
3.1
通讯作者：
Adib-Conquy, Minou
中科院分区：
文献类型：
--
作者：
Adrie, Christophe;Monchi, Mehran;Adib-Conquy, Minou
本研究评估了脑死亡后器官功能障碍的发展中的炎症状态和细胞凋亡激活的作用，使用血浆分析和骨骼肌活检宏阵列分析，以寻找在两个重症监护病房在法国和比利时的远程组织损伤的证据。作为对照，我们使用接受髋关节手术的患者和健康志愿者。研究中纳入的85例连续患者的脑死亡原因为心脏骤停（n = 29; 34%）、卒中（n = 42; 49%，其中38例患者发生出血性卒中）和头部损伤（n = 14; 17%）。在85名患者中，45人捐献了117个器官。血浆内毒素和细胞因子水平表明脑死亡患者存在明显的全身炎症反应，其中心脏骤停组最强。白细胞功能障碍，作为评估的细胞因子的生产响应于各种刺激，注意到在中风后脑死亡的患者亚组。有趣的是，骨骼肌活检显示与炎症相关的基因的mRNA没有增加，而抗凋亡和促凋亡基因的mRNA都增加了，这种平衡有利于凋亡诱导。Western blot进一步证实了促凋亡caspase 9的活化增加。总之，炎症和凋亡诱导的存在可以解释脑死亡后观察到的快速器官功能障碍。这两种异常可能在与脑死亡相关的器官功能障碍中发挥作用。然而，全身炎症水平或循环内毒素的存在与移植物存活率降低无关。
The present study evaluates the role of the inflammatory status and apoptosis activation in the development of organ dysfunction after brain death using plasma assays and macroarray analysis on skeletal muscle biopsies to look for evidence of remote tissue damage in two intensive care units in France and one in Belgium. As controls, we used patients undergoing hip surgery and healthy volunteers. Causes of brain death in the 85 consecutive patients included in the study were cardiac arrest (n = 29; 34%), stroke (n = 42; 49%, with 38 patients having hemorrhagic stroke), and head injury (n = 14; 17%). Of the 85 patients, 45 donated 117 organs. Plasma endotoxin and cytokine levels indicated a marked systemic inflammatory response in brain-dead patients, which was strongest in the cardiac arrest group. Leukocyte dysfunction, as assessed by cytokines production in response to various stimuli, was noted in a subgroup of patients with brain death after stroke. Interestingly, skeletal muscle biopsies showed no increase in mRNAs for genes related to inflammation, whereas mRNAs for both antiapoptotic and proapoptotic genes were increased, the balance being in favor of apoptosis induction. The increased activation of the proapoptotic caspase 9 was further confirmed by Western blot. In conclusion, the presence of inflammation and apoptosis induction may explain the rapid organ dysfunction seen after brain death. Both abnormalities may play a role in organ dysfunction associated with brain death. However, the level of systemic inflammation or the presence of circulating endotoxin was not associated with lower graft survival.