中醫平喘方劑對於過敏原特異性呼吸道發炎反應的作用機轉評估

THE MECHANISMS OF ANTI-ASTHMATIC FORMULAE IN TRADITIONAL CHINESE MEDICINE IN THE TREATMENT OF ALLERGEN-INDUCED AIRWAY INFLAMMATION

傳統醫藥中，有關治療氣喘方藥甚多，常用方劑至少包括小青龍湯（宣肺）、清燥救肺湯（清肺）、瀉白散（瀉肺）、蘇子降氣湯（降肺）和麥門冬湯（潤肺），其作用機轉大部份未明。現代醫學對於氣喘的病理機轉則強調過敏原特異性IgE （Immunoglobulin E） 和第二型CD4 陽性T 淋巴球所分泌的細胞間白素-4（Interleukin-4） ，進而造成呼吸道慢性發炎反應，更進一步則導致呼吸道的過度收縮。因此，本文擬利用現代過敏免疫學的方法，探討傳統平喘方藥的可能作用機轉。本文利用家塵　過敏原特異性動物模式，探討此五種方劑作用於呼吸道發炎反應的可能機轉。使用酵素連結免疫分析法 （ELISA） 測定過敏原特異性IgE 生成，利用肺部病理檢查發炎反應和使用反轉錄　聚合連鎖反應 （Reverse Transcriptase-Polymerase Chain Reaction） 測量細胞間白素-4 在呼吸道中的濃度變化。發現此五種方劑皆無法有效降低過敏原特異性IgE 的生成，但麥門冬湯可顯著調節呼吸道淋巴球細胞間白素-4 的分泌（麥門冬湯組VS 對照組0.65 ±0.3 VS 1.03 ±0.1 ，P<0.01 ），並且有效降低肺部發炎反應。進一步使用反轉錄　聚合連鎖反應亦偵測得到麥門冬湯可降低呼吸道肺泡沖洗液中細胞間白素-4 RNA 的表現，其他方劑則無此顯著效果。因此我們認為麥門冬湯在治療呼吸道過敏發炎反應的可能機轉，主要是經由調降第二型CD4 陽性T 淋巴球發展過敏發炎反應所須要的細胞間白素-4 ，其他平喘方藥的作用機轉則有待更進一步的研究。Several formulas are used in traditional medicine for the treatment of bronchial asthma. Perilla Fruit Qi-Downbearing Decoction (Su Zi Jiang Qi Tang), Green-Blue Dragon Decoction (Qing Long Tang), White-Draining Powder (Xie Bai San), Ophiopogon Decoction (Mai Men Dong Tang) and Dryness-Clearing Lung-Rescuing Decoction (Qing Zao Jin Fei Tang) were commonly prescribed according to the principle of downbearing qi and calming panting, diffusing the lung, draining the lung, moistening the lung and clearing the lung in traditional Chinese medicine respectively. However the mechanisms of these formula are mostly unknown. In modern medicine, the pathogenesis of asthma is attributed to the synthesis of allergenspecific IgE, and the production of interleukin-4 (IL-4) by CD4+ Th2 T lymphocytes. In this study, we tried to clarify the actions of these anti-asthmatic formula by a well-established allergeninduced animal model. Recombinant dust mite allergen, Der p 5 was purified and used to sensitize and challenge BALB/c mice. Allergen-specific IgE was assessed by ELISA and expression of IL-4 RNA was evaluated by RT-PCR in the bronchoaveolar larvage fluids. Inflammation of the airway was examined by pathology. We found that all these 5 formula can not down-regulate the synthesis of allergen-specific IgE, but Ophiopogon can decrease significantly the concentration of interleukin-4 in the bronchoaveolar fluid after allergen-challenge (Ophiopogon group vs control, 0.65 .0.3 vs 1.03 0.1, p<0.01). Ophiopogon Decoction also decreased airway inflammation significantly, compared to other 4 groups. Therefore, we suggest that the mechanisms why Ophiopogon Decoction can treat asthma is partially due to the down-regulation of IL-4 in the lung.