Mahuang decoction mitigates airway inflammation and regulates IL-21/STAT3 signaling pathway in rat asthma model
Mahuang decoction mitigates airway inflammation and regulates IL-21/STAT3 signaling pathway in rat asthma model
复制标题
麻黄汤减轻哮喘模型大鼠气道炎症并调节IL-21/STAT3信号通路
DOI：
10.1016/j.jep.2018.06.011
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发表时间：
2018-10-05
影响因子：
5.4
通讯作者：
Wan, Haitong
中科院分区：
文献类型：
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作者：
He, Yu;Lou, Xiaohui;Wan, Haitong
民族药理学相关性：目前，支气管哮喘仍然是严重威胁人类健康的疾病，寻求有效的治疗药物是我们义不容辞的责任。麻黄汤是我国传统名方，具有化痰止咳、平喘的作用，但其作用机制尚未完全阐明。本研究旨在探讨MHD的抗气道炎症作用及IL 21/STAT 3信号通路可能的分子机制，为MHD治疗支气管哮喘提供理论指导。材料与方法：将无特定病原体的SD大鼠随机分为6组：正常对照组、模型组、阳性药组（复方甲氧那明）、MHD 10 ml/kg、5 ml/kg、2.5ml/kg剂量组，每组10只。除正常对照组外，其余各组均采用卵白蛋白腹腔注射致敏，卵白蛋白吸入激发哮喘模型。末次激发后24 h，取支气管肺泡灌洗液（BALF），用细胞计数法检测炎性细胞数量。ELISA法测定大鼠血清中TXB_2、6-keto-PGF（1 α）、MMP-9、TIMP-1、IL-2、IL-4、IL-5和TNF-α的浓度。Western blotting法检测小鼠肺组织中IL-21、IL-21 R、STAT 3和p-STAT 3的蛋白表达。与对照组相比，模型组小鼠肺组织气道壁和气道平滑肌明显增厚，支气管周围出现大量炎性细胞浸润，BALF中WBC和EOS细胞计数也明显增加，说明成功建立了大鼠哮喘模型。MHD和复方甲氧那明不仅减轻了肺组织的炎症病理损伤，而且还下调了BALF中WBC和EOS的数量。MHD治疗后大鼠血清中TXB_2、MMP-9、TIMP-1、IL-（2、4、5）和TNF-α水平明显降低。Western blotting分析显示，10 ml/kg或5 ml/kg MHD治疗组哮喘大鼠肺组织中IL-21、IL-21 R、STAT 3和p-STAT 3蛋白表达均明显下降至正常水平。MHD干预对哮喘大鼠肺组织炎性介质的分泌及炎性细胞浸润有明显的抑制作用，抑制肺组织IL-21、IL-21 R、STAT 3和p-STAT 3蛋白表达。MHD可有效减轻哮喘大鼠气道炎症，并调节IL-21/STAT 3信号通路。
Ethnopharrnacological relevance: Nowadays, bronchial asthma is still a severe disease threatening human health, and it is incumbent upon us to seek effective therapeutic drugs. Mahuang decoction (MHD), a classic famous Chinese prescription, has been used for thousands of years to prevent phlegm from forming, stop coughing and relieve asthma, but the relevant mechanism has not been thoroughly clarified. This study aims to investigate the anti-airway inflammation effect of MHD and the possible molecular mechanism underlying IL21/STAT3 signaling pathway, so as to provide guidance for the treatment of MHD on bronchial asthma.Materials and methods: Specific pathogen free SD rats were randomly divided into 6 groups: normal control group, model group, positive group (Compound methoxyphenamine), MHD-treated groups at doses of 10 ml/kg, 5 ml/kg and 2.5 ml/kg, 10 rats in each group. Except for the normal control group, rats in other groups were sensitized with ovalbumin via introperitoneal injection and challenged with ovalbumin inhalation to trigger asthma model. At 24 h after the last excitation, bronchoalveolar lavage fluid (BALF) of every rat was drawn and the number of inflammatory cells was analyzed using cell counting method. ELISA method was performed to determine the concentrations of TXB2, 6-keto-PGF(1 alpha) MMP-9, TIMP-1, IL-2, IL-4, IL-5 and TNF-alpha in rat serum. The protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in murine pulmonary tissues were assessed with western blotting analysis.Results: Compared with the control group, the airway wall and airway smooth muscle of murine pulmonary tissues significantly thickened and massive inflammatory cells infiltration occurred around the bronchus in the model group, and the cell counts of WBC and EOS in BALF were also apparently increased, which indicated the rat asthma model was successfully established. MHD or Compound methoxyphenamine not only alleviated the pulmonary inflammatory pathological damages, but also down- regulated the numbers of WBC and EOS in BALF. What's more, the levels of TXB2, MMP-9, TIMP-1, ILs-(2, 4, 5) and TNF-a in rat serum were lessened by the treatment of MHD. In western blotting analysis, treatment with 10 ml/kg or 5 ml/kg MHD markedly declined the increased protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in lung tissues of asthmatic rats to normal level.Conclusion: MHD intervention demonstrated a strong inhibitory action on the secretion of inflammatory mediators as well as the inflammatory cell infiltration in pulmonary tissues of asthmatic rats, and also depressed the protein expressions of IL-21, IL-21R, STAT3 and p-STAT3 in pulmonary tissues. MHD effectively mitigates airway inflammation and regulates the IL-21/STAT3 signaling pathway in rat asthma model.