A myocardial ischemia- and reperfusion-induced injury is mediated by reactive oxygen species released from blood platelets
A myocardial ischemia- and reperfusion-induced injury is mediated by reactive oxygen species released from blood platelets
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心肌缺血和再灌注引起的损伤是由血小板释放的活性氧介导的
DOI：
10.3109/09537104.2012.658107
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发表时间：
2013
期刊：
影响因子：
3.3
通讯作者：
W. Daniel
中科院分区：
文献类型：
--
作者：
C. Seligmann;Gerald Prechtl;M. Kusus;W. Daniel
在最近的实验研究中，发现血小板在缺血和再灌注豚鼠心脏中表现出一些心脏抑制作用，与血栓形成无关。这些影响似乎是由活性氧（ROS）介导的。然而，这些活性氧的来源——血小板或心脏——仍然未知。将进行离体、缓冲液灌注和压力容积工作的豚鼠心脏暴露于持续30分钟的低流量缺血（1ml/分钟），并以5ml/分钟的恒定流量再灌注。在缺血第 15 分钟或再灌注第 1 或第 5 分钟，在凝血酶（0.3U/ml 灌注缓冲液）存在下，以 1 分钟推注（20000 个血小板/μl 灌注缓冲液）给予人血小板。外部心脏做功 (REHW) 的恢复以缺血后和缺血前 EHW 之间的百分比表示。冠状动脉内血小板保留（RET）被量化为所应用的血小板的百分比。在第二组实验中，将血小板与10μM不可逆NADPH氧化酶阻断剂氯化二苯基碘一起孵育，然后洗涤两次，并根据与上述相同的方案进行施用。在凝血酶存在但不应用血小板的情况下暴露于缺血和再灌注的心脏作为对照。未应用血小板的对照并未显示心肌功能的严重损害（REHW 85.5±±1%）。然而，与对照组相比，在缺血期间或再灌注第 1 分钟或第 5 分钟添加血小板导致 REHW 显着降低（REHW 分别为 62.4±6、53.9±3、40.5±3）。使用二苯基氯化碘预处理的血小板的应用没有显示出任何心脏抑制作用，这与未应用血小板的对照有显着不同。此外，用二苯基氯化碘处理血小板并没有显着降低冠状动脉内血小板的滞留。总之，这些结果表明，人血小板在缺血和再灌注豚鼠心脏中的心脏抑制作用是由血小板而不是心脏释放的ROS介导的。
In recent experimental studies, blood platelets have been found to exhibit some cardiodepressive effects in ischemic and reperfused guinea pig hearts independent of thrombus formation. These effects seemed to be mediated by reactive oxygen species (ROS). However, the source of these ROS – platelets or heart – remained still unknown. Isolated, buffer-perfused and pressure-volume work performing guinea pig hearts were exposed to a low-flow ischemia (1 ml/min) of 30 min duration and reperfused at a constant flow of 5 ml/min. Human thrombocytes were administered as 1 min bolus (20 000 thrombocytes/µl perfusion buffer) in the 15th min of ischemia or in the 1st or 5th min of reperfusion in the presence of thrombin (0.3 U/ml perfusion buffer). Recovery of external heart work (REHW) was expressed as ratio between postischemic and preischemic EHW in percent. Intracoronary platelet retention (RET) was quantified as percent of platelets applied. In a second set of experiments, thrombocytes were incubated with 10 µM of the irreversible NADPH oxidase blocker diphenyliodonium chloride and washed twice, thereafter, and administered according to the same protocol as described above. Hearts exposed to ischemia and reperfusion in the presence of thrombin but without application of platelets served as controls. Controls without application of platelets did not reveal a severe compromisation of myocardial function (REHW 85.5 ± 1%). However, addition of platelets during ischemia or in the 1st or 5th min of reperfusion led to a significant reduction of REHW as compared with controls (REHW 62.4 ± 6, 53.9 ± 3, 40.5 ± 3, respectively). Application of platelets pretreated with diphenyliodonium chloride did not reveal any cardiodepressive effects being significantly different from controls without platelet application. Moreover, treatment of platelets with diphenyliodonium chloride did not significantly decrease intracoronary platelet retention. In conclusion, these results demonstrate that cardiodepressive effects of human thrombocytes in ischemic and reperfused guinea pig hearts are mediated by ROS released from thrombocytes and not the heart.