Carbon monoxide promotes gastric wound healing in mice via the protein kinase C pathway
Carbon monoxide promotes gastric wound healing in mice via the protein kinase C pathway
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DOI：
10.1080/10715762.2016.1189546
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发表时间：
2016-06
影响因子：
3.3
通讯作者：
T. Takagi;Y. Naito;K. Uchiyama;Katsura Mizuhima;Takahiro Suzuki;Ryusuke Horie;I. Hirata;H. Tsuboi-H.-T
中科院分区：
文献类型：
--
作者：
T. Takagi;Y. Naito;K. Uchiyama;Katsura Mizuhima;Takahiro Suzuki;Ryusuke Horie;I. Hirata;H. Tsuboi-H.-T
摘要 以往的研究表明，一氧化碳（CO）参与多种生理和病理生理过程，包括抗炎、抗凋亡和抗氧化反应。然而，CO是否促进胃溃疡愈合尚不清楚。在本研究中，我们评估了CO饱和盐水治疗胃溃疡的功效及其潜在机制。使用乙酸在 C57BL/6 雄性小鼠中诱导急性胃溃疡。通过将 50% CO 气体鼓入盐水中来制备 CO 饱和溶液。为了研究CO对胃粘膜愈合的影响，从胃溃疡诱导后第3天开始，每天口服两次CO溶液。溃疡诱导后第7天处死小鼠。切除胃，测量溃疡病灶。体外伤口愈合试验用于确定 CO 在小鼠胃上皮细胞恢复中的作用机制。口服CO溶液通过促进上皮再形成加速胃溃疡愈合。此外，使用小鼠胃上皮细胞进行的伤口愈合测定表明，CO 饱和培养基通过激活蛋白激酶 C (PKC) 增强细胞迁移。基于这些数据，CO可能代表一种治疗胃粘膜损伤的新方法。
Abstract Previous studies have shown that carbon monoxide (CO) is involved in a variety of physiological and pathophysiological processes including anti-inflammatory, anti-apoptotic and anti-oxidant responses. However, it remains unclear whether CO promotes gastric ulcer healing. In the present study, we evaluated the efficacy of CO-saturated saline in the treatment of gastric ulcers and its underlying mechanism. Acute gastric ulcers were induced in C57BL/6 male mice using acetic acid. A CO-saturated solution was prepared by bubbling 50% CO gas into saline. To investigate the effect of CO on gastric mucosal healing, CO solution was orally administrated twice a day beginning on day 3 after the induction of gastric ulcer. Mice were sacrificed on day 7 after ulcer induction. The stomach was removed, and the ulcerated lesions were measured. In vitro wound healing assays were used to determine the mechanism of action of CO in the restoration of murine gastric epithelial cells. The oral administration of CO solution accelerated the gastric ulcer healing by promoting re-epithelialization. Furthermore, the wound healing assay performed using the murine gastric epithelial cells revealed that the CO-saturated medium enhanced cell migration through the activation of protein kinase C (PKC). Based on these data, CO may represent a novel therapeutic approach for the treatment of gastric mucosal injuries.