| 摘要: | 現今對予傳統中醫藥在慢性過敏氣喘中的調節機轉為何知道很少，研究報告也不多。過敏性氣喘（Allergic asthma）是一種慢性氣管發炎疾病，肇因於Th2淋巴細胞反應失調，造成嗜酸性白血球浸潤、肥大細胞活化、上皮細胞肥大、腺細胞活化與增生，導致氣管過度反應及黏液的增加。歐洲室塵蟎Dermatophagoides pteronyssinus（Der p）是目前台灣造成氣喘最主要的原因之一，我們利用隔週連續5次氣管內接種Der p誘發BABL/c小鼠的慢性氣喘動物模型，來探討小青龍湯、苓甘五味薑辛湯、辛夷清肺湯和麻杏石甘湯等四種中醫方劑在治療氣喘方面的機轉。在本實驗中我們發現小青龍湯可以抑制Der p激發小鼠肺泡沖洗液的發炎細胞浸潤、嗜酸性白血球、週邊嗜酸性白血球浸潤、Th2細胞激素(TNFα、TGF-β1、IL-5、IL-6、IL-13)和趨化因子(eotaxin、RANTES、MCP-1 mRNA)的生成。在肺泡沖洗液中小青龍湯增高了Th1細胞激素 IL-12濃度。此外，肺部組織EMSA和免疫組織染色顯示，小青龍湯可以抑制NF-κB的表現。 Collagen沉著分析和H&E染色顯示小青龍湯可以減低呼吸道重塑的情形。經由評估中醫方劑組對塵蟎誘發慢性氣喘小鼠轉錄因子研究中顯示：小青龍湯藉由抑制肺部組織GATA-3表現和脾臟組織c-Maf 表現而調節Th2的發展。苓甘五味薑辛湯降低慢性氣喘發炎反應並減緩呼吸道重塑，主要是選擇性調控單核球和嗜中性白血球，而不是調控嗜酸性白血球。辛夷清肺湯組比小青龍湯組更能抑制塵蟎誘發呼吸道發炎反應與呼吸道重塑作用。辛夷清肺湯組與小青龍湯組在抑制轉錄基因表現不同之處，在於辛夷清肺湯主要抑制肺部組織細胞和脾臟組織細胞中GATA-3表現而調節Th2表現。麻杏石甘湯能降低肺部組織內而非周邊組織的細胞激素、eotaxin和NF-κB的表現。總結而言，本研究希望能解釋寒性方劑和熱性方劑之間的關係，提供中醫師進一步了解如何使用中醫方劑以治療氣喘病患之參考。
Little is known about the mechanism that guides TCM regulation during chronic allergic asthma. Allergic asthma is a chronic airway inflammatory disease, which is characterized by the Th2-bias immune response, eosinophils infiltration, mast cell activation, epithelial hypertrophy, goblet cells hyperplasia, airway hyperresponsiveness, and excessive mucus secretion in the airway. Dermatogoides pteronyssinus（Der p）is one of the most prominent and important species of house dust mite causing allergic asthma in Taiwan. In this study, we used repetitive challenge of Der p it instillation in BABL/c mice as a chronic asthmatic animal model, which helped us to evaluate the therapeutic mechanisms for four Chinese herbal formulas. As a result, we found that XQLT (Xiao-Qing-Long-Tang) remarkably reduced bronchial inflammatory cell infiltration, airway eosinophilia, blood eosinophilia, total IgE levels, Der p-specific IgG1, IL-5, IL-6, IL-13, TNFα, and TGF-β through reducing NF-κB activation as shown by the EMSA, but increase IL-12 in BALF to change Th2-bias. In addition, the results of collagen assays and hematoxylin-eosin staining indicated XQLT could reduce airway remodeling in the lung. Furthermore, the expression of transcriptional factors in herbal formula-treated repeatedly Der p-challenged mice suggests that XQLT modulated Th2 development by suppressing GATA-3 in lung tissue and c-Maf expression in splenocytes. LGWWJXT (Ling-Gang-Wu-Weng-Jiang-Xin-Tang) attenuated Der p-induced airway inflammation and remodeling via selectively regulating on macrophages and neutrophils but not eosinophils in the lungs. XYQFT (Xin-Yi-Qing-Fei-Tang) had more effects than XQLT in the inhibition of airway inflammation and remodeling on repetitive Der p challenged asthmatic mice model. The difference between XYQFT and XQLT is that XYQFT modulates Th2 development by suppression of GATA-3 but not c-Maf expression in the lungs and splenocytes. MXSGT (Ma-Xing-Sin-Gan-Tang) treatment downregulated the expression of cytokines, eotaxin and NF-κB activation in the lungs but not peripheral tissues on repetitive Der p challenged mice. In conclusion, this study result is important in explaining the relationship between cold herbal formula and heat herbal formula, as well as in providing Chinese doctors with a better understanding in the use of herbal formula on asthmatic patients. |
