Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Tangdu Hospital of Fourth Military Medical University, Xi'an, China.
Department of Anesthesiology, Daxing Hospital, Xi'an, China.
J Surg Res. 2020 Feb;246:6-18. doi: 10.1016/j.jss.2019.07.091. Epub 2019 Sep 18.
Remote ischemic postconditioning (RIPost) has been shown to reduce the ischemia-reperfusion injury of the heart and brain. However, the protection mechanisms have not yet been fully elucidated. We have observed that RIPost could alleviate the brain injury after cardiac arrest (CA). The aim of this study was to explore whether α7 nicotinic acetylcholine receptor (α7nAChR) mediates the neuroprotection of RIPost in a rat model of asphyxial CA.
Asphyxial CA model was induced by occlusion of the tracheal tube for 8 min and resuscitated later. RIPost produced by three cycles of 15-min occlusion and 15-min release of the right hind limb by a tourniquet was performed respectively at the moment and the third hour after restoration of spontaneous circulation. The α7nAChR agonist PHA-543613 and the antagonist methyllycaconitine (MLA) were used to investigate the role of α7nAChR in mediating neuroprotective effects.
Results showed that α7nAChR was decreased in hippocampus and cortex after resuscitation, whereas RIPost could attenuate the reduction. The use of PHA-543613 provided neuroprotective effects against cerebral injury after CA. Furthermore, RIPost decreased the levels of neuron-specific enolase, inflammatory mediators, the number of apoptotic cells, and phosphorylation of nuclear factor-κB while increased the phosphorylation of signal transducer and activator of transcription-3. However, the above effects of RIPost were attenuated by α7nAChR antagonist methyllycaconitine.
Neuroprotection of RIPost was related with the activation of α7nAChR, which could suppress nuclear factor-κB and activate signal transducer and activator of transcription-3 in a rat asphyxial CA model.
远程缺血后处理（RIPost）已被证明可以减轻心脏和大脑的缺血再灌注损伤。然而，其保护机制尚未完全阐明。我们观察到 RIPost 可以减轻心脏骤停（CA）后的脑损伤。本研究旨在探讨α7 烟碱型乙酰胆碱受体（α7nAChR）是否介导 RIPost 在窒息性 CA 大鼠模型中的神经保护作用。
通过气管插管阻塞 8 分钟并随后复苏来诱导窒息性 CA 模型。分别在自主循环恢复时和恢复后 3 小时，通过止血带对右后肢进行 3 个周期的 15 分钟闭塞和 15 分钟释放，实施 RIPost。使用 α7nAChR 激动剂 PHA-543613 和拮抗剂甲基烟碱（MLA）来研究 α7nAChR 在介导神经保护作用中的作用。
结果表明，复苏后海马体和皮质中α7nAChR 减少，而 RIPost 可减轻其减少。使用 PHA-543613 可提供针对 CA 后脑损伤的神经保护作用。此外，RIPost 降低了神经元特异性烯醇化酶、炎症介质、凋亡细胞数量和核因子-κB 的磷酸化水平，同时增加了信号转导和转录激活因子 3 的磷酸化。然而，RIPost 的上述作用被 α7nAChR 拮抗剂甲基烟碱减弱。
RIPost 的神经保护作用与 α7nAChR 的激活有关，在窒息性 CA 大鼠模型中，α7nAChR 可抑制核因子-κB 并激活信号转导和转录激活因子 3。
