Department of Emergency Medicine, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
Department of Emergency Medicine, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
J Surg Res. 2019 Dec;244:468-476. doi: 10.1016/j.jss.2019.05.044. Epub 2019 Jul 19.
Targeted temperature management (TTM) is commonly used in hypothermia after cardiopulmonary resuscitation (CPR), and its mechanism to improve cerebral function is complex. This study aimed to investigate the effects of TTM on necroptosis and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in the brain tissue of pigs after CPR.
Ventricular fibrillation was induced, and CPR was performed 10 min later in nine pigs in the normothermia group and nine pigs in the TTM group. The body temperature in the TTM group was dropped to 33°C after CPR and maintained for 24 h, whereas in the normothermia group, it was maintained at 38°C. Before CPR and at 30 h after CPR, serum neuron-specific enolase and S-100β were measured. At 30 h after CPR, pigs were euthanized, and brain tissues were collected for measurement of receptor-interacting protein kinase (RIPIK) 1, RIPK3, mixed lineage kinase domain-like (MLKL), NLRP3, cysteinyl aspartate-specific proteinase (caspase)-1, interleukin (IL)-1β, and IL-18.
Serum neuron-specific enolase and S-100β were increased significantly (P < 0.05) in the two CPR-treated groups compared with the sham group and more obviously in the normothermia group. In addition, the expression of RIPK3, phosphorylated MLKL, and NLRP3 in brain tissues was increased. The expression of RIPK3, phosphorylated MLKL, NLRP3, and caspase-1 as well as the levels of IL-1β and IL-18 were lower (P < 0.05) in the TTM group compared with the normothermia group.
Necroptosis and the NLRP3 pathway were activated after CPR. TTM may attenuate postresuscitation brain injury through the regulation of necroptosis and the NLRP3 pathway.
目标温度管理（TTM）常用于心肺复苏（CPR）后的低温治疗，其改善脑功能的机制较为复杂。本研究旨在探讨 TTM 对 CPR 后猪脑组织坏死性凋亡和 NOD 样受体含pyrin 结构域 3（NLRP3）炎性小体的影响。
在 9 头正常体温组和 9 头 TTM 组猪中诱发心室颤动，CPR 后 10min 进行。CPR 后，TTM 组将体温降至 33°C 并维持 24h，而正常体温组则维持在 38°C。CPR 前和 CPR 后 30h 测量血清神经元特异性烯醇化酶和 S-100β。CPR 后 30h 处死猪，收集脑组织测量受体相互作用蛋白激酶（RIPK）1、RIPK3、混合谱系激酶结构域样（MLKL）、NLRP3、半胱天冬氨酸特异性蛋白酶（caspase）-1、白细胞介素（IL）-1β和 IL-18。
与假手术组相比，两组 CPR 处理组血清神经元特异性烯醇化酶和 S-100β均显著升高（P<0.05），且正常体温组升高更为明显。此外，脑组织中 RIPK3、磷酸化 MLKL 和 NLRP3 的表达增加。与正常体温组相比，TTM 组 RIPK3、磷酸化 MLKL、NLRP3 和 caspase-1 的表达以及 IL-1β和 IL-18 的水平均降低（P<0.05）。
CPR 后坏死性凋亡和 NLRP3 途径被激活。TTM 可能通过调节坏死性凋亡和 NLRP3 途径减轻复苏后脑损伤。
