Yu Qian, Gao Jianbo, Shao Xuebo, Lu Wei, Chen Linling, Jin Lili
Department of Emergency Medicine, The First People's Hospital of Fuyang Hangzhou, Hangzhou, China.
Department of Intensive Care Unit, The First People's Hospital of Fuyang Hangzhou, Hangzhou, China.
Front Med (Lausanne). 2022 May 12;9:892472. doi: 10.3389/fmed.2022.892472. eCollection 2022.
After successful cardiopulmonary resuscitation (CPR), most survivors will develop acute kidney injury and intestinal barrier dysfunction, both of which contribute to the poor outcomes of cardiac arrest (CA) victims. Recently, the aldehyde dehydrogenase 2 (ALDH2) agonist, Alda-1 was shown to effectively alleviate regional ischemia/reperfusion injury of various organs. In the present study, we investigated the effects of Alda-1 treatment on renal and intestinal injuries after CA and resuscitation in pigs.
Twenty-four male domestic pigs were randomly divided into one of the three groups: sham ( = 6), CPR ( = 10), or CPR+Alda-1 ( = 8). CA was induced and untreated for 8 min, and then CPR was performed for 8 min in the CPR and CPR+Alda-1 groups. At 5 min after resuscitation, a dose of 0.88 mg/kg of Alda-1 was intravenously administered in the CPR+Alda-1 group. The biomarkers of renal and intestinal injuries after resuscitation were regularly measured for a total of 24 h. Subsequently, the animals were euthanized, and then renal and intestinal tissues were obtained for the measurements of ALDH2 activity and expression, and cell apoptosis and ferroptosis.
Five of the 10 animals in the CPR group and six of the eight animals in the CPR+Alda-1 group were successfully resuscitated. After resuscitation, the levels of biomarkers of renal and intestinal injuries were significantly increased in all animals experiencing CA and resuscitation compared with the sham group; however, Alda-1 treatment significantly alleviated renal and intestinal injuries compared to the CPR group. Post-resuscitation ALDH2 activity was significantly decreased and its expression was markedly reduced in the kidney and intestine in those resuscitated animals compared with the sham group; nevertheless, both of them were significantly greater in those animals receiving Alda-1 treatment compared to the CPR group. In addition, renal, intestinal apoptosis and ferroptosis after resuscitation were observed in the CPR and CPR+Alda-1 groups, in which both of them were significantly milder in the CPR+Alda1 group than in the CPR group.
The activation of ALDH2 by Alda-1 treatment significantly alleviated post-resuscitation renal and intestinal injuries through the inhibition of cell apoptosis and ferroptosis in a pig model of CA and resuscitation.
在成功进行心肺复苏（CPR）后，大多数幸存者会发生急性肾损伤和肠屏障功能障碍，这两者都会导致心脏骤停（CA）患者预后不良。最近，醛脱氢酶2（ALDH2）激动剂Alda-1被证明能有效减轻各器官的局部缺血/再灌注损伤。在本研究中，我们调查了Alda-1治疗对猪CA及复苏后肾和肠损伤的影响。
将24只雄性家猪随机分为三组之一：假手术组（n = 6）、CPR组（n = 10）或CPR + Alda-1组（n = 8）。在CPR组和CPR + Alda-1组诱导CA并使其持续8分钟未治疗，然后进行8分钟的CPR。复苏后5分钟，CPR + Alda-1组静脉注射0.88 mg/kg的Alda-1。在复苏后的24小时内定期测量肾和肠损伤的生物标志物。随后，对动物实施安乐死，然后获取肾和肠组织以测量ALDH2活性和表达，以及细胞凋亡和铁死亡。
CPR组的10只动物中有5只、CPR + Alda-1组的8只动物中有6只成功复苏。复苏后，与假手术组相比，所有经历CA和复苏的动物肾和肠损伤生物标志物水平均显著升高；然而，与CPR组相比，Alda-1治疗显著减轻了肾和肠损伤。与假手术组相比，复苏后动物肾和肠中的ALDH2活性显著降低，其表达明显减少；尽管如此，与CPR组相比，接受Alda-1治疗的动物中两者均显著更高。此外，在CPR组和CPR + Alda-1组中观察到复苏后肾、肠细胞凋亡和铁死亡，其中CPR + Alda-1组两者均明显轻于CPR组。
在猪CA及复苏模型中，Alda-1治疗激活ALDH2可通过抑制细胞凋亡和铁死亡显著减轻复苏后肾和肠损伤。
