Targeted deletion of regulatory T cells attenuates the protective effects of myocardial ischemic preconditioning in rats
Targeted deletion of regulatory T cells attenuates the protective effects of myocardial ischemic preconditioning in rats
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DOI：
10.3109/14017431.2015.1005661
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发表时间：
2015-01
影响因子：
2.2
通讯作者：
D. Ke;J. Fang;L. Fan;Lianglong Chen
中科院分区：
文献类型：
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作者：
D. Ke;J. Fang;L. Fan;Lianglong Chen
抽象的背景。心肌缺血再灌注损伤(IRI)与先天免疫系统的激活和由此引起的炎症反应有关。心肌缺血预适应(IPC)是对抗心肌缺血再灌注损伤最有效的内源性保护机制，其机制可能与抗炎作用有关。调节性T细胞(Tregs)以转录因子FoxP3的表达为特征，在免疫应答的负性调节中发挥重要作用。我们验证了Tregs可能通过抗炎机制参与心肌IPC保护作用的假说。方法和结果。结扎大鼠冠状动脉左前降支30min，再灌流48h。心肌缺血5分钟再灌流5分钟，共4个循环诱导心肌缺血。结扎左冠状动脉前降支(LAD)造成缺血，松解结扎开始再灌流。IPC后注射去细胞Treg抗体或正常大鼠免疫球蛋白(Ig G)。在IPC后的索引时间点观察到Tregs的积累。心肌FoxP3蛋白表达在IPC后显著增加，在IPC后第2天达到高峰。与免疫球蛋白注射组相比，去除Treg细胞抗体预适应组大鼠心肌FoxP3蛋白表达减少(p<；0.001)，炎性细胞浸润增多(p<；0.001)，心肌梗死范围扩大(p<；0.001)。结论。IPC对心脏的保护作用与Tregs有关。
Abstract Background. Myocardial ischemia-reperfusion injury (IRI) is associated with activation of the innate immune system and the resultant inflammatory response. Myocardial ischemic preconditioning (IPC) is the most powerful endogenous protective mechanism against myocardial IRI, probably via the role of anti-inflammation. Regulatory T cells (Tregs), which are characterized by the expression of the forkhead/winged-helix transcription factor FoxP3, play an important role in the negative modulation of immune responses. We tested the hypothesis that Tregs may contribute to the protective effect of myocardial IPC through anti-inflammatory mechanisms. Methods and results. The left anterior descending coronary arteries of rats were occluded for a 30-min ischemia, followed by a 48-h reperfusion. Myocardial IPC was induced by 4 cycles of 5-min ischemia and 5-min reperfusion. Ischemia was achieved by ligation of the left anterior descending coronary artery (LAD), and reperfusion was initiated by releasing the ligature. Rats were injected with a Treg cell-depleting antibody or normal rat immunoglobulin (IgG), after IPC. The accumulation of Tregs was observed at indexed time points following IPC. The protein expression of FoxP3 significantly increased in the myocardium after IPC, and peaked at day-2. Treatment of preconditioned rats with the Treg cell-depleting antibody demonstrated less protein expression of FoxP3 (p < 0.001), more infiltration of inflammatory cells in the myocardium (p < 0.01), and larger myocardial infarct size (p < 0.001), compared with the IgG injection group. Conclusion. Cardioprotection by IPC is associated with Tregs.