Özyılmaz Ezgi, Büyüknacar Hacer Sinem Göktürk, Bağır Emine Kılıç, Sencar Leman, Öztürk Özlem Görüroğlu, Eray Ismail Cem, Dağlıoğlu Yusuf Kenan, Baydar Oya, Seydaoğlu Gülşah, Mete Ufuk Özgü, Gümürdülü Derya, Kocabaş Ali
Department of Chest Diseases, Faculty of Medicine, Çukurova University, Balcalı, Turkey.
Department of Pharmacology, Faculty of Pharmacy, Çukurova University, Balcalı, Turkey.
Adv Clin Exp Med. 2019 Mar;28(3):291-297. doi: 10.17219/acem/78248.
Recent reports have indicated an improved prognosis in sepsis with β-blocker agents; however, the underlying action mechanism is still under debate.
The aim of this study was to investigate the potential effect of propranolol on endothelial dysfunction in septic rats.
The cecal ligation and puncture model (CLP) was used to generate sepsis. Adult male Wistar-Albino rats were divided into 4 groups: group 1 was a sham group, group 2 received sterile saline, group 3 received 10 mg/kg of propranolol 3 days before the intervention, and group 4 received 10 mg/kg of propranolol 30 min after CLP. Six rats from each group were sacrificed 24 h postoperatively. The remaining rats were followed for survival. We have also evaluated the effects on systemic inflammation, coagulation and the lung tissue with immunohistochemical and electron microscopic evaluation.
Serum tumor necrosis factor alpha (TNF-α) and plasminogen activator inhibitor-1 (PAI-1) levels, as well as tissue TNF-α scores were elevated in septic rats. Electron microscopic examination of the lung tissue showed endothelial dysfunction in the sepsis group. Pretreatment significantly improved survival. Moreover, pre-treatment altered serum vascular endothelial growth factor receptor-1 (VEGFR-1) levels and post-treatment reduced serum PAI-1 and VEGFR-1 levels. In both the preand post-treatment groups, electron microscopic examination revealed improvement of the destroyed lung endothelium and showed only mild alterations in the cytoplasmic organelles, especially in the mitochondria of the endothelial cells.
These results suggest that the improved outcome with β-blockers in sepsis may be due to the ameliorated endothelial dysfunction. Further studies focusing on the potential effect of β-blockers on the endothelium may lead to a better understanding of sepsis.
近期报告显示，使用β受体阻滞剂可改善脓毒症的预后；然而，其潜在作用机制仍存在争议。
本研究旨在探讨普萘洛尔对脓毒症大鼠内皮功能障碍的潜在影响。
采用盲肠结扎穿孔模型（CLP）制备脓毒症模型。成年雄性Wistar - 白化大鼠分为4组：第1组为假手术组，第2组给予无菌生理盐水，第3组在干预前3天给予10 mg/kg普萘洛尔，第4组在CLP后30分钟给予10 mg/kg普萘洛尔。每组6只大鼠在术后24小时处死。其余大鼠观察生存情况。我们还通过免疫组织化学和电子显微镜评估了对全身炎症、凝血和肺组织的影响。
脓毒症大鼠血清肿瘤坏死因子α（TNF-α）和纤溶酶原激活物抑制剂-1（PAI-1）水平以及组织TNF-α评分升高。肺组织电子显微镜检查显示脓毒症组存在内皮功能障碍。预处理显著提高了生存率。此外，预处理改变了血清血管内皮生长因子受体-1（VEGFR-1）水平，治疗后降低了血清PAI-1和VEGFR-1水平。在预处理组和治疗后组中，电子显微镜检查均显示受损的肺内皮有所改善，且细胞质细胞器仅出现轻微改变，尤其是内皮细胞的线粒体。
这些结果表明，β受体阻滞剂改善脓毒症预后可能是由于内皮功能障碍得到改善。进一步关注β受体阻滞剂对内皮的潜在影响的研究可能有助于更好地理解脓毒症。
