伏九贴膏对哮喘小鼠NGF/TrKA及相关炎性因子表达的影响
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摘要
目的观察辽宁中医药大学附属医院制剂"伏九贴膏"对哮喘小鼠血清中白介素4(interleukin-4,IL-4)、干扰素γ(interferon-γ,IFN-γ)、相关免疫球蛋白E (immunoglobulin E,IGE)细胞因子以及肺组织内神经生长因子(nerve growth factor,NGF)和酪氨酸激酶A(tropomyosin receptor kinase A,TrKA)蛋白表达的影响,探讨其治疗哮喘的机制。方法 50只成年BALB/c小鼠随机分为A正常对照组、B哮喘模型组、C地塞米松组、D伏九贴高剂量组、E伏九贴低剂量组5组。卵清蛋白(ovalbumin,OVA)腹腔注射致敏,超声雾化吸入激发,建立哮喘模型。ELISA法检测血清中IL-4、总IGE、OVA特异性IGE和IFN-γ细胞因子的表达,HE染色和Masson染色观察病理改变,免疫组化观察肺组织中NGF、TrKA蛋白表达。结果与正常组相比,模型组NGF、TrkA和IL-4、总IGE、OVA特异性IGE表达均明显升高(P<0. 05),IFN-γ表达降低(P<0. 05);与模型组相比,地塞米松组和伏九贴高剂量组的NGF、TrkA和IL-4、总IGE、OVA特异性IGE表达均降低(P<0. 05),IFN-γ表达升高(P<0. 05),伏九贴膏低剂量组改变均不明显,差异均无统计学意义(P>0. 05)。结论伏九贴膏通过下调NGF、TrKA蛋白的表达,抑制了IL-4、IGE的分泌,同时促进了IFN-γ的分泌,使TH1与TH2趋于平衡,从而缓解哮喘发作。
Objective To explore the effects of a Chinese medicine,"Fujiu plaster"( developed by the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine),on NGF/TrKA and related inflammatory factors in asthmatic mice and its mechanism of action. Methods Fifty SPF adult BALB/c mice were randomly divided into five groups: control,asthma model,dexamethasone,high-dose Fujiu plaster,and low-dose Fujiu plaster groups. To establish the asthma model,the mice were sensitized through intraperitoneal injection of ovalbumin( OVA) and an asthmatic reaction was provoked through ultrasonic aerosol inhalation. Expression of IL-4,total Ig E,OVA-specific Ig E,and IFN-γ in serum was quantified by enzyme-linked immunosorbent assay. Pathological changes were examined using hematoxylin and eosin,and Masson trichrome staining. NGF and TrKA protein expression in the lung tissues was determined using immunohistochemistry. Results Compared with the control group,the model group exhibited significantly increased expression of NGF,Trk A,IL-4,total Ig E,and OVA-specific Ig E( P < 0. 05),but decreased IFN-γ expression( P <0. 05). Compared with the model group,the dexamethasone and high-dose Fujiu plaster groups exhibited significantly reduced expression of NGF,Trk A,IL-4,total Ig E,and OVA-specific Ig E( P < 0. 05),and increased IFN-γ expression( P < 0. 05). No significant changes to the aforementioned indicators were observed in the low-dose Fujiu plaster group( P> 0. 05). Conclusions Fujiu plaster inhibites the secretion of IL-4 and Ig E,and promotes the secretion of IFN-γ by downregulating expression of NGF and Trk A proteins to regulate the imbalance of Th1/Th2 lymphocytes,thus relieving the asthma attack.
Objective To explore the effects of a Chinese medicine,"Fujiu plaster"( developed by the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine),on NGF/TrKA and related inflammatory factors in asthmatic mice and its mechanism of action. Methods Fifty SPF adult BALB/c mice were randomly divided into five groups: control,asthma model,dexamethasone,high-dose Fujiu plaster,and low-dose Fujiu plaster groups. To establish the asthma model,the mice were sensitized through intraperitoneal injection of ovalbumin( OVA) and an asthmatic reaction was provoked through ultrasonic aerosol inhalation. Expression of IL-4,total Ig E,OVA-specific Ig E,and IFN-γ in serum was quantified by enzyme-linked immunosorbent assay. Pathological changes were examined using hematoxylin and eosin,and Masson trichrome staining. NGF and TrKA protein expression in the lung tissues was determined using immunohistochemistry. Results Compared with the control group,the model group exhibited significantly increased expression of NGF,Trk A,IL-4,total Ig E,and OVA-specific Ig E( P < 0. 05),but decreased IFN-γ expression( P <0. 05). Compared with the model group,the dexamethasone and high-dose Fujiu plaster groups exhibited significantly reduced expression of NGF,Trk A,IL-4,total Ig E,and OVA-specific Ig E( P < 0. 05),and increased IFN-γ expression( P < 0. 05). No significant changes to the aforementioned indicators were observed in the low-dose Fujiu plaster group( P> 0. 05). Conclusions Fujiu plaster inhibites the secretion of IL-4 and Ig E,and promotes the secretion of IFN-γ by downregulating expression of NGF and Trk A proteins to regulate the imbalance of Th1/Th2 lymphocytes,thus relieving the asthma attack.
引文
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[13] Qin Q,Wang Z,Pan P,et al. Lung dendritic cells undergo maturation and polarization towards a T helper type 2-stimulating phenotype in a mouse model of asthma:Role of nerve growth factor[J]. Exp Ther Med,2014,8(5):1402-1408.
[14] Zhang XG,Xue Z,Zhao YT,et al. Therapeutic effects of liver soothing pingchuan formula decoction on experimental asthma in BALB/c mice via regulation of nerve growth factor-tyrosine kinase A pathway[J]. Mol Med Rep,2018,17(5):6977-6984.
[15] Shi Y,Jin Y,Guo W,et al. Blockage of nerve growth factor modulates T cell responses and inhibits allergic inflammation in a mouse model of asthma[J]. Inflamm Res,2012,61(12):1369-1378.
[16]张静.神经生长因子对哮喘小鼠肺组织γ-氨基丁酸A受体表达及气道黏液分泌的影响[D].郑州:郑州大学,2013.
[17]欧阳若芸,胡成平,陈平,等.神经生长因子对哮喘大鼠Th1/Th2类细胞因子表达的调控研究[J].中国实用内科杂志,2006,26(20):1613-1616.
[2]全国儿科哮喘协作组.第三次中国城市儿童哮喘流行病学调查[J].中华儿科杂志,2013,51(10):729-736.
[3]蒋沛君,马琳.重症哮喘治疗新进展[J].医药前沿,2018,18(14):38-40.
[4]白晓红,邵功利,王雪峰.伏九贴膏防治小儿哮喘的临床研究探要[J].中华中医药学刊,2004,22(9):1637-1637.
[5]李杰,王雪峰.伏九贴膏的临床研究[J].辽宁中医杂志,2003,30(9):727-728.
[6] Zhu BN,Dong J,Gao X,et al. Antiasthmatic effects of sanglong pingchuan decoction through inducing a balanced th1/th2immune response[J]. Evid Based Complement Alternat Med,2018(14):2629565.
[7]李辉,吴振宇,张云,等.消喘膏穴位贴敷对卵蛋白诱发哮喘大鼠Th1/Th2的调节作用[J].北京中医药大学学报,2012,35(9):623-625.
[8]张玲,虞旻珍,张欣,等.穴位贴敷对变应性鼻炎大鼠IL-4、LTC4的影响[J].中医药学报,2017(6):37-40.
[9] Liu L,Wang LP,He S. Immune homeostasis:Effects of Chinese herbal formulae and herb-derived compounds on allergic asthma in different experimental models[J]. Chin J Integr Med,2018,24(5):390-398.
[10] Fahy JV. Type 2 inflammation in asthma—present in most,absent in many[J]. Nat Rev Immunol,2015,15(1):57-65.
[11]姜丽娜,姚春艳,金齐力,等. Th1型相关细胞因子对人中性粒细胞吞噬功能的影响[J].蚌埠医学院学报,2008,33(3):256-259.
[12] Arredondo LR,Deng C,Ratts RB,et al. Role of nerve growth factor in experimental autoimmune encephalomyelitis[J]. Eur J Immunol,2001,31(2):625-633.
[13] Qin Q,Wang Z,Pan P,et al. Lung dendritic cells undergo maturation and polarization towards a T helper type 2-stimulating phenotype in a mouse model of asthma:Role of nerve growth factor[J]. Exp Ther Med,2014,8(5):1402-1408.
[14] Zhang XG,Xue Z,Zhao YT,et al. Therapeutic effects of liver soothing pingchuan formula decoction on experimental asthma in BALB/c mice via regulation of nerve growth factor-tyrosine kinase A pathway[J]. Mol Med Rep,2018,17(5):6977-6984.
[15] Shi Y,Jin Y,Guo W,et al. Blockage of nerve growth factor modulates T cell responses and inhibits allergic inflammation in a mouse model of asthma[J]. Inflamm Res,2012,61(12):1369-1378.
[16]张静.神经生长因子对哮喘小鼠肺组织γ-氨基丁酸A受体表达及气道黏液分泌的影响[D].郑州:郑州大学,2013.
[17]欧阳若芸,胡成平,陈平,等.神经生长因子对哮喘大鼠Th1/Th2类细胞因子表达的调控研究[J].中国实用内科杂志,2006,26(20):1613-1616.
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