Wang Qianqian, Shen Peng, Zhu Jiangang, Zhu Weidong, Xu Jiefeng
Department of Intensive Care Unit, The First Hospital of Jiaxing, Jiaxing, China.
Department of Emergency Medicine, Traditional Chinese Medical Hospital of Zhuji, Shaoxing, China.
Shock. 2025 Mar 1;63(3):466-473. doi: 10.1097/SHK.0000000000002445. Epub 2024 Aug 2.
Introduction: Intestinal injury is often caused by systemic ischemia-reperfusion injury early after cardiac arrest (CA) and resuscitation. Artesunate (Art) has been confirmed to protect vital organs against diverse of regional I/R injury. This study aimed to investigate the effect of Art on intestinal injury after CA and cardiopulmonary resuscitation (CPR) in swine. Methods: Twenty-two swine were randomly divided into three groups: sham (n = 6), CA/CPR (n = 8), and CA/CPR + Art (n = 8). The CA/CPR swine model was established by inducing 9 min of untreated ventricular fibrillation (VF) followed by 6 min of CPR. Five minutes after resuscitation, 4.8 mg/kg of Art was intravenously administered for 2 h in the CA/CPR + Art group. Intestinal fatty acid-binding protein and diamine oxidase concentrations were compared among the three groups before CA and at 1, 2, 4, and 24 h after resuscitation. At 24 h after resuscitation, intestinal zonula occluden-1 (ZO-1), occludin, apoptosis, caspase-3/gasdermin E (GSDME)-mediated pyroptosis proteins concentrations, and proinflammatory cytokine concentrations were examined to evaluate intestinal injury. Results: During CPR, spontaneous circulation was achieved in seven and six swine in the CA/CPR and CA/CPR + Art groups, respectively. Serum intestinal fatty acid-binding protein and diamine oxidase concentrations were significantly higher and intestinal tissue ZO-1 and occludin concentrations were significantly lower in the CA/CPR and CA/CPR + Art groups than in the sham group. However, Art treatment resulted in markedly improved levels of intestinal injury biomarkers compared with those in the CA/CPR group. Additionally, intestinal apoptosis and concentrations of caspase-3/GSDME-mediated pyroptosis proteins and proinflammatory cytokines were significantly higher in the CA/CPR and CA/CPR + Art groups than in the sham group. However, these variables were significantly lower in the CA/CPR + Art group than in the CA/CPR group. Conclusions: Art treatment effectively alleviates postresuscitation intestinal injury, possibly by inhibiting the caspase-3/GSDME-mediated pyroptosis pathway in a swine CA and CPR model.
心脏骤停（CA）及复苏后早期，肠道损伤常由全身缺血再灌注损伤引起。青蒿琥酯（Art）已被证实可保护重要器官免受多种局部缺血/再灌注损伤。本研究旨在探讨Art对猪CA及心肺复苏（CPR）后肠道损伤的影响。方法：22头猪随机分为三组：假手术组（n = 6）、CA/CPR组（n = 8）和CA/CPR + Art组（n = 8）。通过诱导9分钟未经处理的室颤（VF），随后进行6分钟的CPR建立CA/CPR猪模型。复苏后5分钟，CA/CPR + Art组静脉注射4.8 mg/kg的Art，持续2小时。比较三组在CA前以及复苏后1、2、4和24小时的肠道脂肪酸结合蛋白和二胺氧化酶浓度。复苏后24小时，检测肠道紧密连接蛋白-1（ZO-1）、闭合蛋白、凋亡、半胱天冬酶-3/ Gasdermin E（GSDME）介导的细胞焦亡蛋白浓度以及促炎细胞因子浓度，以评估肠道损伤。结果：CPR期间，CA/CPR组和CA/CPR + Art组分别有7头和6头猪实现自主循环。与假手术组相比，CA/CPR组和CA/CPR + Art组血清肠道脂肪酸结合蛋白和二胺氧化酶浓度显著升高，肠道组织ZO-1和闭合蛋白浓度显著降低。然而，与CA/CPR组相比，Art治疗使肠道损伤生物标志物水平明显改善。此外，与假手术组相比，CA/CPR组和CA/CPR + Art组肠道凋亡、半胱天冬酶-3/ GSDME介导的细胞焦亡蛋白浓度以及促炎细胞因子浓度显著更高。然而，这些变量在CA/CPR + Art组中显著低于CA/CPR组。结论：在猪CA及CPR模型中，Art治疗可有效减轻复苏后肠道损伤，可能是通过抑制半胱天冬酶-3/ GSDME介导的细胞焦亡途径实现的。
