Pakhomova Angelina, Pershina Olga, Bochkov Pavel, Ermakova Natalia, Pan Edgar, Sandrikina Lubov, Dagil Yulia, Kogai Lena, Grimm Wolf-Dieter, Zhukova Mariia, Avdeev Sergey
Laboratory of Regenerative Pharmacology, Goldberg ED Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Centre of the Russian Academy of Sciences, Tomsk 634028, Russia.
NPO Petrovax Pharm LLC, Moscow 123112, Russia.
Life (Basel). 2023 Sep 19;13(9):1932. doi: 10.3390/life13091932.
Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease, characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaze (Bovhyaluronidase Azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaze was administered at different doses by intranasal and intramuscular routes. Histology, hematology, and enzyme-linked immunosorbent assay were used in the study. The use of Longidaze reduced pulmonary fibrosis, as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue, and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaze inhibited the inflammatory response in pulmonary fibrosis, and decreased the levels of IL-6, TNF-α, and hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaze at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaze is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.
特发性肺纤维化（IPF）是间质性肺疾病最常见的形式之一，其特征为进行性肺实质纤维化和呼吸衰竭。在博来霉素诱导的肺纤维化模型中，研究了含有透明质酸酶与高分子量合成载体偶氮溴化物共轭物的龙达泽（Bovhyaluronidase Azoxymer）的抗纤维化和抗炎活性。实验在雄性C57BL/6小鼠中进行。龙达泽通过鼻内和肌肉内途径以不同剂量给药。该研究使用了组织学、血液学和酶联免疫吸附测定法。使用龙达泽可减轻肺纤维化，肺组织病理损伤的改善、结缔组织面积的减少以及肺组织中促纤维化因子（转化生长因子-β1、羟脯氨酸、胶原蛋白I）水平的降低均证明了这一点。此外，龙达泽抑制肺纤维化中的炎症反应，并降低肺组织中白细胞介素-6、肿瘤坏死因子-α和透明质酸的水平以及炎症细胞向肺组织的募集。肌肉注射剂量为120和1200 U/kg的龙达泽时观察到最高治疗效果，其效果优于参比药物艾思瑞（吡非尼酮）。本研究提供的数据表明，龙达泽是一种用于治疗IPF的新型且有前景的药物，值得在纤维化间质性肺疾病患者中进一步研究。
