Влияние финголимода на сурфактант и гемостаз-регулирующую активность лёгких при экспериментальном аутоиммунном энцефаломиелите

M. A. Urakova; I. G. Bryndina

doi:10.25557/2310-0435.2020.04.43-48

M. A. Urakova Izhevsk State Medical Academy, Izhevsk, Russia http://orcid.org/0000-0002-7417-3305
I. G. Bryndina Izhevsk State Medical Academy, Izhevsk, Russia http://orcid.org/0000-0003-4099-4508

DOI: https://doi.org/10.25557/2310-0435.2020.04.43-48

Keywords: pulmonary surfactant, hemostasis-regulating activity of the lung, experimental autoimmune encephalomyelitis, fingolimod

Abstract

Experimental autoimmune encephalomyelitis (EAE) is a common animal model for studying clinical manifestations of multiple sclerosis (MS). Alterations in non-respiratory functions of the lungs in MS is a relevant but understudied issue. A high effectiveness of fingolimod in the treatment of MS has been demonstrated in clinical practice. The aim of this study was to evaluate the effect of fingolimod on the pulmonary surfactant (PS) and the hemostasis-regulating activity of the lungs in EAE.
Methods. Experiments were performed on 95 adult male outbred albino rats. The animals were divided into the following groups: 1, EAE (subcutaneous injections of the encephalitogenic mixture in Freund’s complete adjuvant, n = 25); 2, EAE with intraperitoneal administration of fingolimod (FTY 720, SIGMA, 1 mg/kg, n = 18); 3, intact animals (n = 27); and 4, intraperitoneal administration of Freund’s complete adjuvant without the encephalitogenic mixture (n = 27). Functional and biochemical characteristics of pulmonary surfactant (surface activity, content of total phospholipids and their fractions) and indexes of coagulation hemostasis (APTT and PT) in venous (“before lung”) and arterial (“after lung”) blood were determined.
Results. EAE was associated with a decrease in the content of alveolar phospholipids and changes in their fractional composition, including a decrease in phosphatidylcholine and an increase in lysophosphatidylcholine, which is known to impair the pulmonary surfactant activity. In addition, a hypocoagulative shift in APTT and PT was observed in the “before lung” and “after lung” blood of EAE rats. The fingolimod treatment completely reversed the surfactant changes and partially restored APTT and PT in both arterial and venous blood of animals with EAE.

Conclusion. The results showed a correcting effect of fingolimod on PS and the hemostasis-regulating activity of lungs affected by EAE.

Effect of fingolimod on the surfactant and hemostasis-regulating activity of the lungs in experimental autoimmune encephalomyelitis

Abstract