Federal Research Center of Fundamental and Translational Medicine, Novosibirsk, Russia.
Novosibirsk State Medical University, Ministry of Health of the Russian Federation, Novosibirsk, Russia.
Bull Exp Biol Med. 2020 May;169(1):71-76. doi: 10.1007/s10517-020-04827-4. Epub 2020 Jun 2.
We studied the response of the extracellular matrix of the lungs and liver in mice with BCGinduced granulomatosis (3 months) after inhalation and intraperitoneal administration of liposome-encapsulated dextrazide (LEDZ): a conjugate of oxidized dextran (40 kDa) and isonicotinic acid hydrazide (INH). LEDZ inhalation proved to be more effective in reducing fibrosis severity, both in the lungs and liver. However, the mechanisms of the antifibrotic effect were different: increased degradation and reduced collagen synthesis in the lungs and reduced collagen synthesis and collagen degradation in the liver. This suggest that drug administration routes and delivery to the target organs are crucially important in the therapy of tuberculosis. The antifibrotic effect depended on LEDZ administration route and was more potent after LEDZ inhalation.
我们研究了脂质体包封右旋糖酐(40 kDa)和异烟肼酰肼(INH)缀合物(LEDZ)吸入和腹腔内给药后,BCG 诱导的肉芽肿病(3 个月)小鼠肺部和肝脏细胞外基质的反应。结果表明,LEDZ 吸入在减轻肺部和肝脏纤维化严重程度方面更有效。然而,抗纤维化作用的机制不同:肺部胶原合成减少和胶原降解增加,肝脏胶原合成减少和胶原降解减少。这表明药物给药途径和向靶器官的输送在结核病治疗中至关重要。抗纤维化作用取决于 LEDZ 的给药途径,LEDZ 吸入给药的效果更强。