NOD-like receptor 3 (NLRP3) inflammasome is necessary to initiate acute sterile inflammation. Increasing evidence indicates the activation of NLRP3 inflammasome induced pyroptosis is closely related to reactive oxygen species (ROS) in the sterile inflammatory response triggered by ischemia/reperfusion (I/R) injury. N-acetylcysteine (NAC) is an antioxidant and plays a protective role in local myocardial I/R injury, while its effect on post-resuscitation myocardial dysfunction, as well as its mechanisms, remain elusive. In this study, we aimed to investigate the effect of NAC on post-resuscitation myocardial dysfunction in a cardiac arrest rat model, and whether its underlying mechanism may be linked to ROS and NLRP3 inflammasome-induced pyroptosis. The rats were randomized into three groups: (1) sham group, (2) cardiopulmonary resuscitation (CPR) group, and (3) CPR + NAC group. CPR group and CPR + NAC group went through the induction of ventricular fibrillation (VF) and resuscitation. After return of spontaneous circulation (ROSC), rats in the CPR and CPR + NAC groups were again randomly divided into two subgroups, ROSC 6 h and ROSC 72 h, for further analysis. Hemodynamic measurements and myocardial function were measured by echocardiography, and western blot was used to detect the expression of proteins. Results showed that after treatment with NAC, there was significantly better myocardial function and survival duration; protein expression levels of NLRP3, adaptor apoptosis-associated speck-like protein (ASC), Cleaved-Caspase-1 and gasdermin D (GSDMD) in myocardial tissues were significantly decreased; and inflammatory cytokines levels were reduced. The marker of oxidative stress malondialdehyde (MDA) decreased and superoxide dismutase (SOD) increased with NAC treatment. NAC improved myocardial dysfunction and prolonged animal survival duration in a rat model of cardiac arrest. Moreover, possibly by partly inhibiting ROS-mediated NLRP3 inflammasome-induced pryoptosis.

中文翻译：

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N-乙酰半胱氨酸通过部分抑制 NLRP3 炎性体诱导的细胞焦亡来缓解复苏后心肌功能障碍并改善生存结果。

NOD 样受体 3 (NLRP3) 炎性体是引发急性无菌性炎症所必需的。越来越多的证据表明，NLRP3 炎症小体诱导的细胞焦亡与缺血/再灌注 (I/R) 损伤引发的无菌炎症反应中的活性氧 (ROS) 密切相关。N-乙酰半胱氨酸 (NAC) 是一种抗氧化剂，在局部心肌 I/R 损伤中起保护作用，而其对复苏后心肌功能障碍的影响及其机制仍不清楚。在这项研究中，我们旨在研究 NAC 对心脏骤停大鼠模型中复苏后心肌功能障碍的影响，以及其潜在机制是否可能与 ROS 和 NLRP3 炎症小体诱导的细胞焦亡有关。将大鼠随机分为三组：（1）假手术组，(2)心肺复苏(CPR)组，(3)CPR+NAC组。CPR组和CPR+NAC组分别进行了心室颤动（VF）的诱导和复苏。自主循环恢复（ROSC）后，再次将CPR组和CPR+NAC组大鼠随机分为ROSC 6 h和ROSC 72 h两个亚组进行进一步分析。超声心动图测量血流动力学和心肌功能，Western blot检测蛋白表达。结果显示，经NAC治疗后，心肌功能和生存期明显改善；心肌组织中NLRP3、适配器凋亡相关斑点样蛋白（ASC）、Cleaved-Caspase-1和gasdermin D（GSDMD）的蛋白表达水平显着降低；和炎症细胞因子水平降低。随着NAC处理，氧化应激丙二醛（MDA）的标志物减少，超氧化物歧化酶（SOD）增加。NAC 在心脏骤停大鼠模型中改善了心肌功能障碍并延长了动物存活时间。此外，可能通过部分抑制 ROS 介导的 NLRP3 炎性体诱导的细胞凋亡。