Abstract:

Objective To explore the effects of imperatorin （IMP） on airway remodeling in the bronchial asthma mice， and to elucidate the possible mechanisms. Methods Forty SFP male BALB/c mice were randomly divided into control group， model group， low dose of IMP group （IMP-L group）， high dose of IMP group （IMP-H group） and dexamethasone group， with 8 mice in each group. Except for contol group， the mice in the other groups were injected with an ovalbumin （OVA） suspension intraperitoneally to induce the asthma models. After one week， the daily asthma symptoms of the mice were observed and scored. After 8 weeks， the enhanced pause（Penh） values of the mice in various groups were detected to evaluate the airway reactivities. The percentages of eosinophils in the bronchoalveolar lavage fluid （BALF） of the mice in various groups were detected by flow cytometry. The levels of serum IgE， interleukin interferon-gamma（IL）-13， IL-5， IL-4 and interferon-gamma（IFN-γ） in BALF of the mice in various groups were measured by enzyme-linked immunosorbent assay （ELISA） method. HE， PAS and Masson staining were applied to observe the pathomorphology， the number of goblet cells and collagen deposition of the lung tissue of the mice in various groups.Immunohisto chemistry method was applied to detect the expressions of α-smooth muscle actin （α-SMA） and mouse mammary tumor virus（MMTV） wingless type MMTV intergration site family member 5A （Wnt5A） proteins in lung tissue of the mice in various groups. The expression levels of Wnt5A， cellular myelocytomatosis oncogene （c-Myc）， β-catenin and α-SMA in lung tissue of the mice in various groups were detected by Western blotting method. The expression levels of α-SMA protein in lung tissue of the mice in various groups were detected by immunofluorescence method. Results Compared with control group， the score of asthma symptoms of the mice in model group was increased （P<0.01）； the Penh value was significantly increased （P<0.01）； the serum IgE levels and the levels of IL-13， IL-5， IL-4 in BALF， as well as the percentage of eosinophils （EOS） in BALF were significantly increased （P<0.05 or P<0.01）， and the level of IFN-γ was reduced （P<0.05）； the expression levels of α-SMA and Wnt5A proteins in lung tissue were markedly increased （P<0.01）； the expression levels of proteins associated with the Wnt/β-catenin signaling pathway in the lung tissue were significantly increased （P<0.01）； the immofluorescence method results showed the expression level of α-SMA protein in lung tissue was significantly increased （P<0.01）. Compared with model group， the scores of asthma symphtoms of the mice in IMP-L group， IMP-H group， and dexamethasone group were decereased （P<0.01）， and the Penh values of the mice in IMP-H group were decreased （P<0.05）； the serum IgE levels and the levels of IL-13， IL-5， IL-4 in BALF， as well as the percentages of EOS in BALF of the mice in IMP-L group， IMP-H group， and dexamethasone group were decreased （P<0.05 or P<0.01）， and the levels of IFN-γ were increased （P<0.05）； the expression levels α-SMA and Wnt5A proteins in lung tissue were decreased （P<0.05 or P<0.01）； the expression levels of proteins related to the Wnt/β-catenin signaling pathway in the lung tissue were decreased （P<0.05 or P<0.01）； the immunofluorescence method results showed that expression levels of the α-SMA protein in the lung tissue were reduced （P<0.05 or P<0.01）. Conclusion IMP has an improving effect on airway remodeling in the asthmatic mice and can inhibit the expression levels of Wnt/β-catenin pathway-related proteins.

Key words: Imperatorin, Asthma, Airway remodeling, Wnt/β-catenin signaling pathway, α-smooth muscle actin