Hemorrhagic shock and resuscitation (HSR) can induce severe intestinal damages, thereby leading to sepsis and long-term complications including dysbacteriosis and pulmonary injury. The NOD-like receptor protein 3 (NLRP3) inflammasome facilitates inflammation-associated cell recruitment in the gastrointestinal tract, and participates in many inflammatory bowel diseases. Previous studies have shown that exogenous carbon monoxide (CO) exerts neuroprotective effects against pyroptosis after HSR. We aimed to investigate whether carbon monoxide-releasing molecules-3 (CORM-3), an exogenous CO compound, could attenuate HSR-induced intestinal injury and the potential underlying mechanism.Rats were subjected to a HSR model by bleeding and re-infusion. Following resuscitation, 4 mg/kg of CORM-3 was administered intravenously into femoral vein. At 24 h and 7 d after HSR modeling, the pathological changes in intestinal tissues were evaluated by H&E staining. The intestinal pyroptosis, glial fibrillary acidic protein (GFAP)-positive glial pyroptosis, DAO (diamine oxidase) content, intestine tight junction proteins including zonula occludens-1 (ZO-1) and claudin-1 were further detected by immunofluorescence, western blot and chemical assays at 7 d after HSR. CORM-3 administration led to significantly mitigated HSR-induced intestinal injury, aggravation of intestinal pyroptosis indicated by cleaved caspase-1, IL-1β and IL-18, upregulation of GFAP-positive glial pyroptosis, decreased intensity of ZO-1 and claudin-1 in the jejunum, and increased of DAO in the serum. Nigericin, an agonist of NLRP3, significantly reversed the protective effects of CORM-3. CORM-3 alleviates the intestinal barrier dysfunction in a rodent model of HSR, and the potential mechanism may be associated with inhibition of NLRP3-associated pyroptosis. CORM-3 administration could be a promising therapeutic strategy for intestinal injury after hemorrhagic shock.

失血性休克和复苏（HSR）可引起严重的肠道损伤，从而导致败血症和长期并发症，包括菌群失调和肺损伤。NOD 样受体蛋白 3 (NLRP3) 炎症小体促进胃肠道中炎症相关细胞的募集，并参与许多炎症性肠病。先前的研究表明，外源性一氧化碳 (CO) 对 HSR 后的细胞焦亡发挥神经保护作用。我们的目的是研究外源性 CO 化合物一氧化碳释放分子 3 (CORM-3) 是否可以减轻 HSR 诱导的肠道损伤及其潜在机制。 通过放血和回输的方式对大鼠进行 HSR 模型。复苏后，将4mg/kg的CORM-3静脉注射至股静脉中。HSR造模后24 h和7 d,采用H&E染色评价肠组织病理变化。通过免疫荧光、蛋白质印迹和免疫印迹法进一步检测肠道焦亡、胶质纤维酸性蛋白（GFAP）阳性胶质细胞焦亡、DAO（二胺氧化酶）含量、肠道紧密连接蛋白包括闭合小带-1（ZO-1）和claudin-1。 HSR后7天进行化学测定。CORM-3 给药可显着减轻 HSR 诱导的肠道损伤，裂解 caspase-1、IL-1β 和 IL-18 表明肠道焦亡加剧，GFAP 阳性神经胶质细胞焦亡上调，ZO-1 和密蛋白强度降低空肠中DAO增加1，血清中DAO增加。Nigericin 是 NLRP3 的激动剂，可显着逆转 CORM-3 的保护作用。CORM-3 可减轻 HSR 啮齿动物模型中的肠道屏障功能障碍，其潜在机制可能与抑制 NLRP3 相关的细胞焦亡有关。CORM-3 给药可能是失血性休克后肠道损伤的一种有前途的治疗策略。