Department of Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey.
Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2019 Feb;392(2):135-145. doi: 10.1007/s00210-018-1571-8. Epub 2018 Oct 24.
Sepsis is a life-threatening organ dysfunction condition response resulting in acute lung injury. Urotensin II (UII), an endogenous vasoactive peptide, is widely distributed in pulmonary, cardiovascular, central nervous, renal and metabolic systems, and especially in inflammatory regions. This study aimed to investigate whether urotensin II (UII) and UII receptor (UTR) antagonists play a role in the inflammatory response to sepsis-induced lung damage and they are possible therapeutic targets. In the study, 78 male Balb-c mice were used. A cecal ligation and puncture (CLP)-induced polymicrobial sepsis model was applied, and the effects of human urotensin II (agonist) and urantide and palosuran (antagonists) were investigated on lung tissues. Glutathione and malondialdehyde levels and SOD activity of lung tissues were investigated in addition to TNF-α, IL-1β, IL-6, NF-κB, and UTR mRNA levels. Also, lung sections were histopathologically evaluated. Urantide and palosuran, UII receptor antagonists, decreased proinflammatory cytokines such as TNF-α, IL-1β, IL-6, NF-κB, and also decreased oxidative stress parameters in lung tissue, which are markers of damage. UTR mRNA expression was increased in septic lungs, and both antagonists significantly decreased the elevated receptor level. Also, histopathological examination showed beneficial effects of both agonists on lung tissue. The results of this study help to understand the inflammatory and therapeutic contribution of the UII/UTR system on sepsis-induced lung damage. We can suggest that UTR receptor antagonists may be evaluated as a potential drug which reduces sepsis-induced lung damage in the future.
脓毒症是一种危及生命的器官功能障碍疾病，可导致急性肺损伤。尾加压素 II（UII）是一种内源性血管活性肽，广泛分布于肺、心血管、中枢神经系统、肾脏和代谢系统，尤其是在炎症区域。本研究旨在探讨尾加压素 II（UII）和 UII 受体（UTR）拮抗剂是否在脓毒症诱导的肺损伤的炎症反应中发挥作用，以及它们是否可能成为治疗靶点。在这项研究中，使用了 78 只雄性 Balb-c 小鼠。应用盲肠结扎穿孔（CLP）诱导的多微生物脓毒症模型，研究了人尾加压素 II（激动剂）和乌瑞替肽和 palosuran（拮抗剂）对肺组织的影响。此外，还研究了肺组织的谷胱甘肽和丙二醛水平以及 SOD 活性、TNF-α、IL-1β、IL-6、NF-κB 和 UTR mRNA 水平。还对肺组织进行了组织病理学评估。Urantide 和 palosuran 是 UII 受体拮抗剂，可降低 TNF-α、IL-1β、IL-6、NF-κB 等促炎细胞因子，以及肺组织中的氧化应激参数，这些都是损伤的标志物。UTR mRNA 在脓毒症肺中表达增加，两种拮抗剂均显著降低了升高的受体水平。此外，组织病理学检查显示两种激动剂对肺组织均有有益作用。本研究的结果有助于了解 UII/UTR 系统对脓毒症诱导的肺损伤的炎症和治疗作用。我们可以建议，UTR 受体拮抗剂将来可能被评估为一种减轻脓毒症诱导的肺损伤的潜在药物。
