EFFECT OF ARTESUNATE TREATMENT ON INTESTINAL INJURY AFTER CARDIOPULMONARY RESUSCITATION IN SWINE.

IF 2.7 3区医学 Q2 CRITICAL CARE MEDICINE SHOCK Pub Date : 2025-03-01 Epub Date: 2024-08-02 DOI:10.1097/SHK.0000000000002445

Qianqian Wang, Peng Shen, Jiangang Zhu, Weidong Zhu, Jiefeng Xu

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Abstract

Abstract: 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.

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青蒿琥酯治疗对猪心肺复苏后肠道损伤的影响。

导言：肠道损伤通常是由心脏骤停（CA）和复苏后早期的全身缺血再灌注损伤引起的。青蒿琥酯（Art）已被证实可保护重要器官免受多种区域性 I/R 损伤。本研究旨在探讨青蒿琥酯对猪心脏骤停和心肺复苏（CPR）后肠道损伤的影响：22头猪被随机分为三组：假组（n = 6）、CA/CPR组（n = 8）和CA/CPR + Art组（n = 8）。CA/CPR 猪模型是通过诱导 9 分钟未处理的心室颤动（VF），然后进行 6 分钟心肺复苏建立的。复苏后 5 分钟，在 CA/CPR + Art 组中静脉注射 4.8 mg/kg Art，持续 2 小时。比较了 CA 前、复苏后 1、2、4 和 24 小时三组患者的肠道脂肪酸结合蛋白（iFABP）和二胺氧化酶（DAO）浓度。在复苏后 24 小时，检测肠闭塞带-1（ZO-1）、闭塞素、细胞凋亡、Caspase-3/gasdermin E（GSDME）介导的热蛋白浓度和促炎细胞因子浓度，以评估肠道损伤：在心肺复苏过程中，CA/CPR 组和 CA/CPR + Art 组分别有 7 头和 6 头猪实现了自主循环。与假组相比，CA/CPR 组和 CA/CPR + Art 组的血清 iFABP 和 DAO 浓度明显更高，肠组织 ZO-1 和闭塞素浓度明显更低。然而，与 CA/CPR 组相比，Art 治疗明显改善了肠道损伤生物标志物的水平。此外，CA/CPR组和CA/CPR + Art组的肠道凋亡以及由Caspase-3/GSDME介导的热蛋白和促炎细胞因子的浓度均显著高于假体组。然而，这些变量在 CA/CPR + Art 组明显低于 CA/CPR 组：结论：在猪 CA 和心肺复苏模型中，艺术治疗可有效缓解复苏后的肠道损伤，这可能是通过抑制 caspase-3/GSDME 介导的热蛋白沉积途径实现的。

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来源期刊

SHOCK 医学-外科

CiteScore

6.20

自引率

3.20%

发文量

199

审稿时长

1 months

期刊介绍： SHOCK®: Injury, Inflammation, and Sepsis: Laboratory and Clinical Approaches includes studies of novel therapeutic approaches, such as immunomodulation, gene therapy, nutrition, and others. The mission of the Journal is to foster and promote multidisciplinary studies, both experimental and clinical in nature, that critically examine the etiology, mechanisms and novel therapeutics of shock-related pathophysiological conditions. Its purpose is to excel as a vehicle for timely publication in the areas of basic and clinical studies of shock, trauma, sepsis, inflammation, ischemia, and related pathobiological states, with particular emphasis on the biologic mechanisms that determine the response to such injury. Making such information available will ultimately facilitate improved care of the traumatized or septic individual.