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阿德米多醇:一种治疗肺纤维化的新型、有前景的抗氧化和抗炎治疗手段。

Adelmidrol: A New Promising Antioxidant and Anti-Inflammatory Therapeutic Tool in Pulmonary Fibrosis.

作者信息

Fusco Roberta, Cordaro Marika, Genovese Tiziana, Impellizzeri Daniela, Siracusa Rosalba, Gugliandolo Enrico, Peritore Alessio Filippo, D'Amico Ramona, Crupi Rosalia, Cuzzocrea Salvatore, Di Paola Rosanna

机构信息

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy.

Department of Biomedical, Dental and Morphological and Functional Imaging University of Messina, Via Consolare Valeria, 98125 Messina, Italy.

出版信息

Antioxidants (Basel). 2020 Jul 9;9(7):601. doi: 10.3390/antiox9070601.

Abstract

BACKGROUND

Chronic pulmonary diseases are characterized by airway remodeling due to complex multicellular responses and the production of free oxygen radicals. They lead to a progressive decline of pulmonary functions. Adelmidrol is an analogue of palmitoylethanolamide (PEA), which is a well-known anti-inflammatory and anti-oxidant compound. In this study, we investigated the efficacy of adelmidrol (10 mg/Kg) for bleomycin-induced pulmonary fibrosis in mice.

METHODS

Bleomycin intratracheal administration was performed on the first day and for the following twenty-one days, mice were treated with adelmidrol (10 mg/Kg).

RESULTS

The survival rate and body weight gain were recorded daily. At the end of the experiment, adelmidrol-administered animals showed reduced airway infiltration by inflammatory cells, Myeloperoxidase (MPO) activity, and pro-inflammatory cytokine overexpression (IL,6 IL-1β, TNF-α, and TGF-1β). Moreover, adelmidrol treatment was able to manage the significant incapacity of antioxidants and elevation of the oxidant burden, as shown by the MDA, SOD, and GSH levels and decreased nitric oxide production. It was also able to significantly modulate the JAK2/STAT3 and IκBα/NF-kB pathway. Histologic examination of the lung tissues showed reduced sample injury, mast cell degranulation, chymase activity, and collagen deposition.

CONCLUSIONS

In sum, our results propose adelmidrol as a therapeutic approach in the treatment of pulmonary fibrosis.

摘要

背景

慢性肺部疾病的特征是由于复杂的多细胞反应和游离氧自由基的产生导致气道重塑。它们会导致肺功能逐渐下降。阿德米多醇是棕榈酰乙醇胺(PEA)的类似物,PEA是一种著名的抗炎和抗氧化化合物。在本研究中,我们研究了阿德米多醇(10毫克/千克)对博来霉素诱导的小鼠肺纤维化的疗效。

方法

在第一天进行博来霉素气管内给药,在接下来的21天里,用阿德米多醇(10毫克/千克)治疗小鼠。

结果

每天记录存活率和体重增加情况。在实验结束时,接受阿德米多醇治疗的动物炎症细胞气道浸润减少,髓过氧化物酶(MPO)活性降低,促炎细胞因子过度表达(IL-6、IL-1β、TNF-α和TGF-1β)受到抑制。此外,阿德米多醇治疗能够改善抗氧化剂的显著不足和氧化负担的升高,这通过丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)水平以及一氧化氮生成减少得以体现。它还能够显著调节JAK2/STAT3和IκBα/NF-κB信号通路。肺组织的组织学检查显示样本损伤减轻、肥大细胞脱颗粒、糜酶活性降低以及胶原沉积减少。

结论

总之,我们的结果表明阿德米多醇可作为治疗肺纤维化的一种治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd97/7402091/323140372c2a/antioxidants-09-00601-g001.jpg

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