Bu-Shen-Yi-Qi formulae Suppresses Chronic Airway Inflammation and Regulates Th17/Treg imbalance in the Murine Ovalbumin Asthma Model
Research backgroud: Bu-Shen-Yi-Qi formulae (BSYQF) is frequently used in the treatment of chronic inflammatory diseases in the respiratory system such as asthma and chronic obstructive pulmonary disease (COPD) in traditional Chinese medicine (TCM).However,the regulatory effect of BSYQF on T helper 17 (Thl7) and regulatory T (Treg) cells in murine ovalbumin (OVA) asthma model remains poorly understood.In the present study,we sought to determine the effect of high-performance liquid chromatography/mass spectrometry (HPLC/MS) standardized BSYQF on chronic airway inflammation and Thl7/Treg imbalance in the murine OVA asthma model.Materials and Methods: The murine asthma model was induced by OVA sensitization and challenge,and BSYQF was oral administrated the day before the first OVA inhalation for eight weeks.24h after last OVA exposure,airway hyperresponsiveness (AHR) to methacholine (Mch) was assessed by an invasive method using Buxco equipment,and inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were analysed by five classification method.Histopathological evaluation of the lung was performed by hematoxylin and eosin (H&E) and periodic acid-schiff (PAS) staining.Thl7 and Treg associated cytokine levels in serum and BALF as well as transcription factors expression in the lung tissue were measured by ELISA,Bio-Plex and western blot assay.We also analysed the CD4+RORγ t+ and CD4+Foxp3+ T cells in BALF and spleen by flow cytometric analysis.Results: Our results demonstrated that oral administration of BSYQF inhibited the markedly increased AHR and lung inflammation in murine OVA asthma model (p < 0.05) and BSYQF (10g and 20g) had the same potential to that of DEX (p > 0.05).BALF cells analysis revealed that total inflammatory cells which included neutrophils (Neu),lymphocytes (Lym),monocytes (Mon),eosinophils (Eos) and basophils (Bas) increased remarkably after long term OVA challenge in murine asthma model (p < 0.05).BSYQF and DEX treatment resulted in a dramatic reduction in total inflammatory cells as well as Neu,Lym,Mon,Eos and Bas (p < 0.05).BSYQF had more obvious efficacy in reducing total inflammatory cells and Lym.Furthermore,BSYQF (20g) was more effective than DEX in reducing Neu and Mon in BALF of murine asthma (p < 0.05).IL-6,IL-10 and IL-17A levels in serum elevated distinctly in murine asthma,and a reduced IL-6,IL-10 and IL-17A levels in serum were observed in BSYQF treated groups (p < 0.05).IL-6 and IL10 levels were particularly decreased and TGF-1β1 and IL-17A were markedly increased in BALF of murine OVA asthma (p < 0.05).After BSYQF and DEX treatment,the expression of IL-6 and ILl0 increased and TGF-β1 and IL-17A decreased prominently (p < 0.05).Significantly increased protein expression of Th17 transcript factor RORγt and decreased Treg transcript factor Foxp3 was observed in the lung tissue of asthmatic mice (p < 0.05),and BSYQF treatment reversed this expression mode remarkable (p < 0.05).Flow cytometry analysis revealed that CD4+RORγt+ T cells in BALF and spleen elevated markedly in murine OVA asthma model (p < 0.05),and BSYQF and DEX treatment lead to an obvious reduction in CD4+RORγt+ T cells in BALF (p < 0.05) but not in spleen.OVA inhalation induced a prominent decrease in CD4+Foxp3+ T cells in BALF and spleen in murine OVA asthma model (p < 0.05),and BSYQF and DEX treatment resulted in an obvious elevation in CD4+Foxp3+ T cells in BALF and spleen (p < 0.05).Conclusions: Collectively,these results demonstrated that BSYQF could suppress chronic airway inflammation and regulate Thl7/Treg imbalance in the murine OVA asthma model,which may help to elucidate the underlying regulatory mode of BSYQF on asthma treatment.
Ying Wei Qing-Li Luo Jing Sun Mei-Xia Chen Feng Li Jing-Cheng Dong
Department of Integrative Medicine,Huashan Hospital,Fudan University,12Middle Urumqi Road,Shanghai,200040,China;Institute of Integrated Traditional Chinese and Western Medicine,Fudan University,12 Middle Urumqi Road,Shanghai,200040,China
国内会议
第三届民族传统医学与现代医学国际学术大会暨第十三次全国中西医结合防治呼吸系统疾病学术研讨会
西宁
英文
271-273
2014-10-23（万方平台首次上网日期，不代表论文的发表时间）