Survival and outcome of cardiac arrest (CA) are dismal despite improvements in cardiopulmonary resuscitation (CPR). Salvianolic acid B (Sal B), extracted from Salvia miltiorrhiza, has been investigated for its cardioprotective properties in cardiac remodeling and ischemic heart disease, but less is known about its role in CA. The aim of this study was to learn whether Sal B improves cardiac and neurologic outcomes after CA/CPR in mice. Female C57BL/6 mice were subjected to eight minutes of CA induced by an intravenous injection of potassium chloride (KCl), followed by CPR. After 30 seconds of CPR, mice were blindly randomized to receive either Sal B (20 mg/kg) or vehicle (normal saline) intravenously. Hemodynamic variables and indices of left ventricular function were determined before CA and within three hours after CPR, the early postresuscitation period. Sal B administration resulted in a remarkable decrease in the time required for the return of spontaneous circulation (ROSC) in animals that successfully resuscitated compared to the vehicle-treated mice. Myocardial performance, including cardiac output and left ventricular systolic (dp/dt_max) and diastolic (dp/dt_min) function, was clearly ameliorated within three hours of ROSC in the Sal B-treated mice. Moreover, Sal B inhibited CA/CPR-induced cardiomyocyte apoptosis and preserved mitochondrial morphology and function. Mechanistically, Sal B dramatically promoted Nrf2 nuclear translocation through the downregulation of Keap1, which resulted in the expression of antioxidant enzymes, including HO-1 and NQO1, thereby counteracted the oxidative damage in response to CA/CPR. The aforementioned antiapoptotic and antioxidant effects of Sal B were impaired in the setting of gene silencing of Nrf2 with siRNA in vitro model. These improvements were associated with better neurological function and increased survival rate (75% vs. 40%, ) up to 72 hours postresuscitation. Our findings suggest that the administration of Sal B improved cardiac function and neurological outcomes in a murine model of CA via activating the Nrf2 antioxidant signaling pathway, which may represent a novel therapeutic strategy for the treatment of CA.

中文翻译：

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丹酚酸B改善了心脏骤停的小鼠模型中的复苏后心肌和脑预后：Nrf2信号通路的参与。

尽管心肺复苏（CPR）有所改善，但心脏骤停（CA）的存活率和预后却令人沮丧。从丹参中提取的丹酚酸B（Sal B）因其在心脏重塑和缺血性心脏病中的心脏保护作用而被研究，但对其在CA中的作用知之甚少。这项研究的目的是了解Sal B是否能改善小鼠CA / CPR后的心脏和神经功能。通过静脉内注射氯化钾（KCl）诱导雌性C57BL / 6小鼠八分钟的CA，然后进行CPR。CPR 30秒后，将小鼠盲目随机接受静脉注射Sal B（20 mg / kg）或赋形剂（生理盐水）。在CA之前和CPR后三个小时内确定血流动力学变量和左心室功能指标，复苏后的早期。与赋形剂处理的小鼠相比，Sal B的使用可显着减少成功复苏的动物自发循环（ROSC）返回所需的时间。心肌表现，包括心输出量和左心室收缩（dp / dt在用Sal B治疗的小鼠中，ROSC的三小时内，_max（_最大）和舒张功能（dp / dt _min）的功能明显改善。此外，Sal B抑制CA / CPR诱导的心肌细胞凋亡并保持线粒体的形态和功能。在机制上，Sal B通过下调Keap1显着促进Nrf2核易位，从而导致抗氧化酶（包括HO-1和NQO1）的表达，从而抵消了对CA / CPR的氧化损伤。Sali B的上述抗凋亡和抗氧化作用在siRNA体外模型沉默Nrf2基因的设置中被削弱。这些改善与更好的神经系统功能和更高的生存率相关（75％对40％，），复苏后最多72小时。我们的发现表明，通过激活Nrf2抗氧化剂信号传导途径，Sal B的给药改善了CA小鼠模型的心脏功能和神经系统结局，这可能代表了CA治疗的新治疗策略。