Qin Jingbo, Lv Mingsheng, Jiang Zeqiang, Meng Xianghe, Wang Yi, Cui Jiarui, Wang Ji, Wang Qi
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine (BUCM), Beijing, China.
Respiratory Department, BUCM Third Affiliated Hospital, Beijing, China.
Front Pharmacol. 2021 Sep 22;12:725953. doi: 10.3389/fphar.2021.725953. eCollection 2021.
Allergic asthma is a stubborn chronic inflammatory disease, and is considered a co-result of various immune cells, especially mast cells, eosinophils and T lymphocytes. At present, the treatment methods of allergic asthma are limited and the side effects are obvious. Traditional Chinese medicine has been used to treat diseases for thousands of years in China. One such example is the treatment of allergic asthma, which take the characteristics of less adverse reactions and obvious curative effect. Tuo-Min-Ding-Chuan Decoction (TMDCD) is a traditional Chinese medicine compound for the treatment of allergic asthma optimized from Ma-Xing-Gan-Shi Decoction (MXGSD), which was put forward in Treatise on Febrile Diseases by Zhang Zhongjing in the Eastern Han Dynasty. The compound shows a significant clinical effect, but the mechanism of its influence on the immune system is still unclear. The purpose of this study was to observe whether TMDCD could alleviate the symptoms of ovalbumin (OVA) challenged allergic asthma mice, and to explore its immune regulatory mechanism, especially on mast cell (MC) degranulation. The results showed TMDCD could not only reduce the airway hyperresponsiveness (AHR), inflammatory cell infiltration and mucus secretion in the lung tissue of OVA challenged mice, but also decrease the levels of total IgE, OVA-specific IgE, histamine and LTC4 in serum. We found that TMDCD can downregulate the expression of Fractalkine, Tryptase ε, IL-25, CCL19, MCP-1, OX40L, Axl, CCL22, CD30, G-CSF, E-selectin, OPN, CCL5, P-selectin, Gas6, TSLP in OVA challenged mice serum by using mouse cytokines antibody array. It has been reported in some literatures that these differentially expressed proteins are related to the occurrence of allergic asthma, such as tryptase ε, MCP-1, CCL5, etc. can be released by MC. And the results of experiments showed that TMDCD inhibited the degranulation of RBL-2H3 cells stimulated by DNP-IgE/BSA. Taken together, we made the conclusion that TMDCD could reduce the infiltration of inflammatory cells in lung tissue and alleviate airway remodeling in mice with allergic asthma, showed the effects of anti-inflammatory and antiasthmatic. TMDCD could also reduce the levels of IgE, histamine, LTC4, Tryptase ε, and other MC related proteins in the serum of allergic asthma mice, and the experiments showed that TMDCD could inhibit IgE mediated degranulation and histamine release of RBL-2H3 cells, proved its anti allergic effect.
过敏性哮喘是一种顽固的慢性炎症性疾病，被认为是多种免疫细胞共同作用的结果，尤其是肥大细胞、嗜酸性粒细胞和T淋巴细胞。目前，过敏性哮喘的治疗方法有限且副作用明显。中医在中国已有数千年的治病历史。其中一个例子就是用于治疗过敏性哮喘，其具有不良反应少、疗效显著的特点。脱敏定喘汤（TMDCD）是一种从东汉张仲景《伤寒论》中的麻杏甘石汤（MXGSD）优化而来的用于治疗过敏性哮喘的中药复方。该复方显示出显著的临床效果，但其对免疫系统的影响机制仍不清楚。本研究的目的是观察脱敏定喘汤是否能减轻卵清蛋白（OVA）激发的过敏性哮喘小鼠的症状，并探讨其免疫调节机制，特别是对肥大细胞（MC）脱颗粒的影响。结果表明，脱敏定喘汤不仅能降低OVA激发小鼠肺组织的气道高反应性（AHR）、炎症细胞浸润和黏液分泌，还能降低血清中总IgE、OVA特异性IgE、组胺和白三烯C4（LTC4）的水平。我们发现，通过使用小鼠细胞因子抗体芯片，脱敏定喘汤可以下调OVA激发小鼠血清中趋化因子、类胰蛋白酶ε、白细胞介素-25（IL-25）、CC趋化因子配体19（CCL19）、单核细胞趋化蛋白-1（MCP-1）、OX40配体（OX40L）、AXL受体酪氨酸激酶（Axl）、CC趋化因子配体22（CCL22）、CD30分子、粒细胞集落刺激因子（G-CSF）、E选择素、骨桥蛋白（OPN）、CC趋化因子配体5（CCL5）、P选择素、生长停滞特异性蛋白6（Gas6）、胸腺基质淋巴细胞生成素（TSLP）的表达。一些文献报道，这些差异表达的蛋白质与过敏性哮喘的发生有关，如类胰蛋白酶ε、MCP-1、CCL5等可由肥大细胞释放。实验结果表明，脱敏定喘汤可抑制二硝基苯基化免疫球蛋白E（DNP-IgE）/牛血清白蛋白（BSA）刺激的大鼠嗜碱性粒细胞白血病细胞（RBL-2H3细胞）脱颗粒。综上所述，我们得出结论，脱敏定喘汤可减少过敏性哮喘小鼠肺组织炎症细胞浸润，减轻气道重塑，具有抗炎、平喘作用。脱敏定喘汤还可降低过敏性哮喘小鼠血清中IgE、组胺、LTC4、类胰蛋白酶ε等与肥大细胞相关蛋白的水平，且实验表明脱敏定喘汤可抑制IgE介导的RBL-2H3细胞脱颗粒和组胺释放，证明其抗过敏作用。
