Zhang Zhongyuan, Liang Meifeng, Wan Xiongfei
Department of Pharmacy, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei 430060, P.R. China.
Department of Medical Insurance and Management, CR & WISCO General Hospital, Wuhan, Hubei 430000, P.R. China.
Exp Ther Med. 2021 Dec;22(6):1398. doi: 10.3892/etm.2021.10834. Epub 2021 Oct 1.
Sepsis is a systemic inflammatory response syndrome caused by infection, which has a complex mechanism. The gastrointestinal tract is commonly the first organ affected by sepsis, but intestinal disease itself can also induce sepsis. Roflumilast has been found to exert anti-inflammatory effects and, thus, the present study sought to examine its effect on intestinal damage caused by sepsis. studies were conducted using cecal ligation and puncture rat models, and experiments were performed using IEC-6 cells. The intestinal cells were first induced with lipopolysaccharide and the induced cells were then treated with roflumilast to evaluate its effects on phosphodiesterase (PDE)4 expression, intestinal function indices, release of inflammatory factors and cell apoptosis. The expression level of PDE4 in the small intestinal tissue of septic rats was found to be significantly higher compared with that in the normal group, suggesting that PDE4 may play a key role in intestinal injury caused by sepsis. It was found that roflumilast reduced PDE4 expression, as well as the levels of intestinal function indices, including lactate dehydrogenase, diamino oxidase and intestinal fatty acid-binding protein, in intestinal cells. Moreover, roflumilast reduced cellular damage, the release of inflammatory factors and apoptosis. In summary, the findings of the present study indicated that roflumilast can relieve the inflammation and apoptosis of intestinal cells caused by sepsis and can promote their functional recovery. These findings may promote the expansion of the clinical application of roflumilast in the future.
脓毒症是一种由感染引起的全身炎症反应综合征，其机制复杂。胃肠道通常是脓毒症首先累及的器官，但肠道疾病本身也可诱发脓毒症。已发现罗氟司特具有抗炎作用，因此，本研究旨在探讨其对脓毒症所致肠道损伤的影响。采用盲肠结扎穿孔大鼠模型进行研究，并使用IEC-6细胞进行实验。首先用脂多糖诱导肠细胞，然后用罗氟司特处理诱导后的细胞，以评估其对磷酸二酯酶（PDE）4表达、肠道功能指标、炎症因子释放和细胞凋亡的影响。发现脓毒症大鼠小肠组织中PDE4的表达水平明显高于正常组，提示PDE4可能在脓毒症所致肠道损伤中起关键作用。结果发现，罗氟司特可降低肠细胞中PDE4的表达，以及肠道功能指标的水平，包括乳酸脱氢酶、二胺氧化酶和肠脂肪酸结合蛋白。此外，罗氟司特可减轻细胞损伤、炎症因子释放和细胞凋亡。总之，本研究结果表明，罗氟司特可减轻脓毒症所致肠细胞的炎症和凋亡，并可促进其功能恢复。这些发现可能会推动罗氟司特未来临床应用范围的扩大。
