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一种5型磷酸二酯酶(PDE-5)抑制剂西地那非可减轻坏死性小肠结肠炎诱导的炎症。

A Phosphodiesterase Type-5 (PDE-5) Inhibitor, Sildenafil, Ameliorates the NEC Induced Inflammation.

作者信息

Ovalı Mehmet Akif, Öztopuz Özlem, Karaboğa İhsan

机构信息

Faculty of Medicine, Department of Physiology, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.

Faculty of Medicine, Department of Biophysics, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.

出版信息

Protein J. 2025 Mar 8. doi: 10.1007/s10930-025-10263-y.

Abstract

The connection between intestine microbiota and lung disease is described as the gut-lung axis, these organ systems are somehow interrelated in both homeostasis and disease development. In newborns, the most important gastrointestinal complications are necrotizing enterocolitis (NEC), and the pulmonary complication both cause significant systemic morbidity. In this study, sildenafil administered at varying doses in neonatal rat model of experimental necrotizing enterocolitis and focused on both mRNA expression and histopathological alterations. 15-day-old Wistar Albino rat pups were randomly divided into six groups; Control, NEC, DMSO, Sil_1mg, Sil_5mg, Sil_10mg (n = 5). NEC induction was performed using hypoxia/asphyxia and cold stress. At the end of the experiment, lung tissues were harvested, molecular and histopathological alterations were analysed. Histopathological examination was performed with hematoxylin&eosin and masson trichrome staining in lung samples of neonatal rats and the mRNA expression levels of TNF-α, IL-6 and HSPa5 genes were analyzed. The mRNA expression levels of TNF-α, IL-6 and HSPa5 were increased in the NEC group compared to the control group and sildenafil treatment could significantly reduced the levels of the genes and inflammation (*p < 0.05 and **p ≤ 0.0001). Alveolar edema and hemorrhage findings were observed in the lung tissue of the NEC group. Interstitial edema and hemorrhage findings were reduced in the groups treated with sildenafil compared to the NEC group. The data we obtained indicate that sildenafil administering at different doses has therapeutic effect on NEC induced lung tissue inflammation both at the mRNA expression and tissue levels.

摘要

肠道微生物群与肺部疾病之间的联系被描述为肠-肺轴,这些器官系统在稳态和疾病发展过程中都存在某种程度的相互关联。在新生儿中,最重要的胃肠道并发症是坏死性小肠结肠炎(NEC),而肺部并发症都会导致显著的全身发病率。在本研究中,在实验性坏死性小肠结肠炎的新生大鼠模型中给予不同剂量的西地那非,并关注mRNA表达和组织病理学改变。将15日龄的Wistar白化病大鼠幼崽随机分为六组:对照组、NEC组、二甲基亚砜组、西地那非1mg组、西地那非5mg组、西地那非10mg组(n = 5)。使用缺氧/窒息和冷应激诱导NEC。实验结束时,采集肺组织,分析分子和组织病理学改变。对新生大鼠肺样本进行苏木精和伊红染色以及马松三色染色进行组织病理学检查,并分析TNF-α、IL-6和HSPa5基因的mRNA表达水平。与对照组相比,NEC组中TNF-α、IL-6和HSPa5的mRNA表达水平升高,而西地那非治疗可显著降低这些基因的水平和炎症(*p < 0.05和**p≤0.0001)。在NEC组的肺组织中观察到肺泡水肿和出血现象。与NEC组相比,用西地那非治疗的组间质水肿和出血现象减少。我们获得的数据表明,不同剂量的西地那非给药在mRNA表达和组织水平上对NEC诱导的肺组织炎症均具有治疗作用。

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