Inhalation of simvastatin attenuates airway inflammation in mice of asthma model
10.16438/j.0513-4870.2017-0098
- VernacularTitle:雾化吸入不同剂量辛伐他汀对哮喘模型小鼠气道炎症的影响
- Author:
Lan XU
1
;
Yun SUN
2
Author Information
1. The First Hospital of Wujiang, Suzhou 215200, China
2. Yangzhou University Medical Academy, Yangzhou 225001, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
airway inflammation;
simvastatin;
inhalation;
drug delivery route;
asthma
- From:
Acta Pharmaceutica Sinica
2017;52(8):1250-1254
- CountryChina
- Language:Chinese
-
Abstract:
The impact of statins on airway inflammation has not yet been established and it may differ from their cholesterol-lowering effects. Oral administration of statins at large-doses may have adverse effects. It is possible to overcome the side effect to increase the clinical efficacy through the inhalation route. Female BALB/c mice were randomly divided into four groups including the control group (NS-vehicle), model group[ovalbumim (OVA)-vehicle], simvastatin (Sim) group and dexamethasone (DXM) group at 10 mice in each group. In this study, we hypothesize Sim as a potential anti-inflammatory drug with biological and pharmacokinetic properties suitable for delivery through the inhalation route. Mice were immunized with OVA and then challenged with OVA aerosol to induce the asthma reaction. Sim was inhaled at a dosage (5 mg ·mL-1, ih, 15 min) or administrated by intraperitoneal injection (40 mg·kg-1, ip) or gavage (40 mg·kg-1, ig) during the OVA-challenge. In the mouse model of asthma, Sim significantly attenuated the total inflammatory cell counts and eosinophil counts (P< 0.01 or P<0.05) via the different routes. Pretreatment with Sim at 1, 5, 20 mg·mL-1, ih, significantly decreased the total inflammatory cell counts and eosinophil counts in alveolar lavage fluid (BALF) (P< 0.01) and the inhibitory effect was increased with the dosages of Sim via inhalation. Both of DXM and Sim at 5, 20 mg·mL-1, ih, were more potent than that of Sim at 1 mg·mL-1, ih. Sim significantly decreased IL-4 and IL-5 mRNA expression of lung at 5, 20 mg·mL-1, ih (P< 0.01 or P<0.05). Sim (5, 20 mg·mL-1, ih) significantly decreased levels of IL-4 and IL-5 in BALF (P < 0.01 or P < 0.05). However, Sim (1 mg·mL-1) declined slightly on IL-4 level in BALF. Sim at 5, 20 mg·mL-1 had a greater rate of decline in IL-5 than at 1 mg·mL-1. These results suggest Sim with different doses as a potential anti-inflammatory drug for airway inflammatory diseases with properties suitable for delivery by inhalation, which probably overcome the side effects and low clinical efficacy of oral Sim.
