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甘草酸可减轻小鼠实验性过敏性哮喘。

Glycyrrhizin alleviates experimental allergic asthma in mice.

作者信息

Ram Arjun, Mabalirajan U, Das Moumita, Bhattacharya Indranil, Dinda Amit K, Gangal Sharad V, Ghosh Balaram

机构信息

Molecular Immunogenetics Laboratory, Institute of Genomics and Integrative Biology, Mall Road, Delhi-110007, India.

出版信息

Int Immunopharmacol. 2006 Sep;6(9):1468-77. doi: 10.1016/j.intimp.2006.04.020. Epub 2006 Jun 6.

Abstract

Asthma is a chronic respiratory disease, the incidence of which is increasing globally. The existing therapy is inadequate and has many adverse effects. It needs a better therapeutic molecule preferably of natural origin, which has negligible or no adverse effects. In view of this, we evaluated Glycyrrhizin (GRZ), a major constituent of a plant Glycyrrhiza glabra, for its efficacy on asthmatic features in a mouse model of asthma. BALB/c mice were sensitized and challenged with ovalbumin (OVA) to develop the asthmatic features such as airway hyperresponsiveness: allergen induced airway constriction and airway hyperreactivity (AHR) to methacholine (MCh), and pulmonary inflammation. The mice were orally treated with GRZ (2.5, 5, 10 and 20 mg/kg) during or after OVA-sensitization and OVA-challenge to evaluate its protective or reversal effect, respectively on the above asthmatic features. The status of airway hyperresponsiveness was measured by monitoring specific airway conductance (SGaw) using a non-invasive method and the pulmonary inflammation was assessed by haematoxylin and eosin staining of lung sections. Several other parameters associated with asthma such as interleukin (IL)-4, IL-5 interferon-gamma (IFN-gamma), OVA-specific IgE, total IgG(2a) and cortisol were measured by ELISA. GRZ (5 mg/kg) markedly inhibited OVA-induced immediate airway constriction, AHR to MCh (p<0.01), lung inflammation, and infiltration of eosinophils in the peribronchial and perivascular areas. It prevented the reduction of IFN-gamma (p<0.02), and decreased IL-4 (p<0.05), IL-5 (p<0.05) and eosinophils (p<0.0002) in the BAL fluid. Also, it reduced OVA-specific IgE levels (p<0.01) and prevented the reduction of total IgG(2a) (p<0.01) in serum. We have also showed that it has no effect on serum cortisol levels. Our results demonstrate that GRZ alleviates asthmatic features in mice and it could be useful towards developing a better therapeutic molecule in the future.

摘要

哮喘是一种慢性呼吸道疾病,其发病率在全球范围内呈上升趋势。现有的治疗方法并不充分,且有许多不良反应。因此需要一种更好的治疗分子,最好是天然来源的,其不良反应可忽略不计或没有不良反应。鉴于此,我们评估了光果甘草的主要成分甘草甜素(GRZ)对哮喘小鼠模型哮喘特征的疗效。用卵清蛋白(OVA)对BALB/c小鼠进行致敏和激发,以诱发哮喘特征,如气道高反应性:变应原诱导的气道收缩和对乙酰甲胆碱(MCh)的气道高反应性(AHR),以及肺部炎症。在OVA致敏期间或之后以及OVA激发后,分别用GRZ(2.5、5、10和20mg/kg)对小鼠进行口服治疗,以评估其对上述哮喘特征的保护或逆转作用。通过使用非侵入性方法监测比气道传导率(SGaw)来测量气道高反应性状态,并通过对肺切片进行苏木精和伊红染色来评估肺部炎症。通过酶联免疫吸附测定法测量与哮喘相关的其他几个参数,如白细胞介素(IL)-4、IL-5、干扰素-γ(IFN-γ)、OVA特异性IgE、总IgG(2a)和皮质醇。GRZ(5mg/kg)显著抑制OVA诱导的即刻气道收缩、对MCh的AHR(p<0.01)、肺部炎症以及支气管周围和血管周围区域嗜酸性粒细胞的浸润。它可防止IFN-γ的降低(p<0.02),并降低BAL液中的IL-4(p<0.05)、IL-5(p<0.05)和嗜酸性粒细胞(p<0.0002)。此外,它降低了血清中OVA特异性IgE水平(p<0.01),并防止了总IgG(2a)的降低(p<0.01)。我们还表明它对血清皮质醇水平没有影响。我们的结果表明,GRZ可减轻小鼠的哮喘特征,并且在未来开发更好的治疗分子方面可能会有用。

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