AOS ameliorates monocrotaline-induced pulmonary hypertension by restraining the activation of P-selectin/p38MAPK/NF-κB pathway in rats

Perivascular inflammation, vascular luminal area reduction and hemodynamics changes are important pathophysiologic bases of pulmonary hypertension (PH). In this study, PH was induced by an intraperitoneal single injection of monocrotaline (MCT, 60 mg/kg). Alginate oligosaccharides (AOS), one of the most famous marine drugs, provided protections in the perivascular inflammation, vascular luminal area reduction and hemodynamics changes of the PH rat induced by MCT. The downregulation of P-selectin plays an important role in the protective effects of AOS against MCT induced PH. The results showed that the treatment with AOS (5, 10, or 20 mg/kg) dose-dependently decreased the expression of P-selectin in serum, pulmonary tissue and pulmonary artery of MCT-induced pulmonary arterial hypertension rats. What's more, the study showed that the protective effects were mediated by the inhibition of p38MAPK/NF-κB pathway, which was caused by reducing the p-p38MAPK protein expression, IκBα degradation and nuclear transcription of NF-κB protein in the pulmonary artery of MCT-induced PH rats. These findings provided an alternative potent medicine for the prevention and therapy of PH.