The inhalation of carbon monoxide (CO) gas and the administration of CO-releasing molecules were shown to inhibit the development of intestinal inflammation in a murine colitis model. However, it remains unclear whether CO promotes intestinal wound healing. Herein, we aimed to evaluate the therapeutic effects of the topical application of CO-saturated saline enemas on intestinal inflammation and elucidate the underlying mechanism. Acute colitis was induced with trinitrobenzene sulfonic acid (TNBS) in male Wistar rats. A CO-saturated solution was prepared via bubbling 50% CO gas into saline and was rectally administrated twice a day after colitis induction; rats were sacrificed 3 or 7 days after induction for the study of the acute or healing phases, respectively. The distal colon was isolated, and ulcerated lesions were measured. In vitro wound healing assays were also employed to determine the mechanism underlying rat intestinal epithelial cell restitution after CO treatment. CO solution rectal administration ameliorated acute TNBS-induced colonic ulceration and accelerated ulcer healing without elevating serum CO levels. The increase in thiobarbituric acid-reactive substances and myeloperoxidase activity after induction of acute TNBS colitis was also significantly inhibited after CO treatment. Moreover, the wound healing assays revealed that the CO-saturated medium enhanced rat intestinal epithelial cell migration via the activation of Rho-kinase. In addition, the activation of Rho-kinase in response to CO treatment was confirmed in the inflamed colonic tissue. Therefore, the rectal administration of a CO-saturated solution protects the intestinal mucosa from inflammation and accelerates colonic ulcer healing through enhanced epithelial cell restitution. CO may thus represent a novel therapeutic agent for the treatment of inflammatory bowel disease.

在小鼠结肠炎模型中，吸入一氧化碳 (CO) 气体和施用 CO 释放分子可抑制肠道炎症的发展。然而，目前尚不清楚CO是否促进肠道伤口愈合。在此，我们的目的是评估局部应用CO饱和盐水灌肠对肠道炎症的治疗效果并阐明其潜在机制。用三硝基苯磺酸 (TNBS) 在雄性 Wistar 大鼠中诱导急性结肠炎。通过将50％CO气体鼓泡到盐水中来制备CO饱和溶液，并在结肠炎诱导后每天两次直肠给药；诱导后3天或7天处死大鼠，分别用于急性期或愈合期的研究。分离远端结肠，并测量溃疡病变。体外伤口愈合测定也用于确定 CO 处理后大鼠肠上皮细胞恢复的机制。 CO 溶液直肠给药可改善 TNBS 诱导的急性结肠溃疡并加速溃疡愈合，且不会升高血清 CO 水平。 CO治疗后诱导急性TNBS结肠炎后硫代巴比妥酸反应物质和髓过氧化物酶活性的增加也受到显着抑制。此外，伤口愈合试验表明，CO 饱和培养基通过激活 Rho 激酶增强大鼠肠上皮细胞迁移。此外，在发炎的结肠组织中证实了 Rho 激酶响应 CO 处理而被激活。 因此，直肠给予CO饱和溶液可以保护肠粘膜免受炎症的影响，并通过增强上皮细胞的恢复来加速结肠溃疡的愈合。因此，CO可能代表一种治疗炎症性肠病的新型治疗剂。