[Therapeutic effects of glycyrrhizic acid on asthma airway inflammation in mice and its mechanism].
キーワード
概要
OBJECTIVE
To explore the therapeutic effects and mechanism of glycyrrhizic acid (GA) on airway inflammation in a murine model of asthma.
METHODS
A total of 70 female BALB/c mice were randomly divided into 5 groups (n = 14 each) of control, asthmatic and three treatments with low, medium and high doses of GA. Mice in the asthmatic and the treatment groups were sensitized and challenged by ovalbumin (OVA). Mice of the treatment groups were injected intraperitoneally with GA (25, 50, 100 mg/kg) 30 min before each OVA challenge. The control mice received an aerosol inhalation of normal saline instead of OVA. Within 24 hours after the last OVA challenge, bronchoalveolar lavage fluid (BALF) was collected for counting total cells and eosinophils (Eos) in other 8 mice in each group. Interleukin (IL)-12p70, IL-10, IL-4 and interferon gamma (IFN-γ ) were measured in BALF by enzyme-linked immunosorbent assay (ELISA). Histological studies of lung were conducted with hematoxylin and eosin staining (HE) and the expressions of CD86, major histocompatibility complex (MHC)-II, CD40, OX40 ligand (OX40L) on CD11c(+) dendritic cells (DCs) in spleens were evaluated with flow cytometry (FCM).
RESULTS
Compared with the control group, the number of total cells and eosinophils was higher in BALF in asthmatic group ((124.3 ± 39.7)×10(7)/L, (26.3 ± 17.2)×10(7)/L vs (55.3 ± 22.8)×10(7)/L, (0.6 ± 0.4) ×10(7)/L), the expressions of IL-10 and IL-4 increased ((49 ± 12, 169 ± 29) ng/L vs (34 ± 4, 89 ± 37) ng/L) and the levels of IFN-γ and IFN-γ/IL-4 ratio decreased in BALF ((122 ± 56 ) ng/L, (0.7 ± 0.4) vs (89 ± 37) ng/L, 2.9 ± 0.8)), the expressions of CD86, MHC-II, CD40, OX40L on CD11c(+) DCs increased in spleens ((38.4 ± 15.7)%, (90.4 ± 3.4)%, (25.4 ± 10.2)%, (29.6 ± 9.9)% vs (18.8 ± 4.4)%, (73.1 ± 11.3)%, (3.8 ± 2.2)%, (5.0 ± 1.6)%) (all P < 0.05). Compared with the asthmatic group, total cell counts and the eosinophil numbers significantly decreased by the treatment of GA at a dose of 100 mg/kg ( (62.1 ± 21.7)×10(7)/L, (2.2 ± 1.7)×10(7)/L), the levels of IL-12p70, IL-10, IFN-γ and the ratio of IFN-γ/IL-4 increased ((44 ± 14, 132 ± 13, 208 ± 66) ng/L, (1.8 ± 0.6)) and the level IL-4 decreased (122 ± 38) ng/L. The expressions of MHC-II, CD40, OX40L on CD11c(+) DCs decreased ((75.8 ± 15.9)%, (11.1 ± 5.9)%, (11.8 ± 3.4)%)) (all P < 0.05). The asthmatic mice induced an infiltration of inflammatory cells around airways and blood vessels. Administration of GA significantly reduced the infiltration of inflammatory cells in peribronchial areas compared with asthmatic mice especially at a dose of 50 mg/kg 100 mg/kg.
CONCLUSIONS
GA effectively ameliorates the airway inflammation of asthma via inhibiting the Th2 responses though modulating the expressions of CD86, MHC-II, CD40, OX40L on CD11c(+) DCs.
