Ohba Reina, Otaka Michiro, Odashima Masaru, Jin Mario, Komatsu Koga, Konishi Noriaki, Wada Isao, Horikawa Youhei, Matsuhashi Tamotsu, Oyake Jinko, Hatakeyama Natsumi, Watanabe Sumio
Department of Internal Medicine, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
J Gastroenterol. 2006 Jan;41(1):34-40. doi: 10.1007/s00535-005-1686-9.
Cilostazol, a specific type-III phosphodiesterase inhibitor, is widely used for the treatment of ischemic symptoms of peripheral vascular disease. Recent studies have reported that the mechanism of cilostazol is related to the suppression of pro-inflammatory cytokine production and improvement of local microcirculation disturbances. The pathogenesis of stress-induced gastric mucosal lesions is characterized by the activation of inflammatory cells and the production of inflammatory cytokines. The effects of cilostazol on the development of gastric mucosal lesions have not been reported. In the present study, we examined the effect of a cilostazol on water-immersion stress-induced gastric mucosal lesions.
Rats were subjected to water-immersion stress with or without pretreatment with a single intraperitoneal injection of the selective type-III phosphodiesterase inhibitor, cilostazol. We measured the gastric mucosal lesion and the concentrations of myeloperoxidase (MPO), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1), as an index of neutrophil accumulation and pro-inflammatory cytokine production.
Cilostazol ameliorated the gastric mucosal injury induced by water-immersion stress (P<0.001). The gastric contents of MPO, TNF-alpha, IL-1beta, and CRO/CINC-1 were all increased after water-immersion stress and were reduced to almost normal levels by cilostazol.
In this study, we demonstrated that a selective type-III phosphodiesterase inhibitor, cilostazol, inhibited stress-induced gastric inflammation and damage via suppressing the production of pro-inflammatory cytokines. Cilostazol may be useful for preventing gastric mucosal lesions.
西洛他唑是一种特异性III型磷酸二酯酶抑制剂，广泛用于治疗外周血管疾病的缺血症状。最近的研究报道，西洛他唑的作用机制与抑制促炎细胞因子的产生和改善局部微循环障碍有关。应激性胃黏膜损伤的发病机制以炎症细胞的激活和炎症细胞因子的产生为特征。西洛他唑对胃黏膜损伤发展的影响尚未见报道。在本研究中，我们检测了西洛他唑对水浸应激诱导的胃黏膜损伤的影响。
大鼠接受水浸应激，其中一组在腹腔注射选择性III型磷酸二酯酶抑制剂西洛他唑进行预处理，另一组未进行预处理。我们测量了胃黏膜损伤以及髓过氧化物酶（MPO）、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）和细胞因子诱导的中性粒细胞趋化因子-1（GRO/CINC-1）的浓度，作为中性粒细胞聚集和促炎细胞因子产生的指标。
西洛他唑改善了水浸应激诱导的胃黏膜损伤（P<0.001）。水浸应激后，MPO、TNF-α、IL-1β和CRO/CINC-1的胃内含量均升高，而西洛他唑将其降低至几乎正常水平。
在本研究中，我们证明了选择性III型磷酸二酯酶抑制剂西洛他唑通过抑制促炎细胞因子的产生来抑制应激诱导的胃炎症和损伤。西洛他唑可能有助于预防胃黏膜损伤。
