黃芩苷抗哮喘作用與HMGB1/TLR4傳導通路的相關性研究

韓超 楊柳 張秋玲 梁慧玲 徐俊

摘要 目的：研究黃芩苷對支氣管哮喘防治的作用及其可能的作用機制。方法：將54只SD大鼠按體質量隨機分為正常組、哮喘模型組、地塞米松組及黃芩苷高、低劑量組。用卵清蛋白（OVA）誘發致敏大鼠建立支氣管哮喘的動物模型，給予相應藥物灌胃給藥4周，1次/d，其中正常組及哮喘模型組藥物以等量生理鹽水代替。用藥物干預性治療后，觀察各組藥物對大鼠的哮喘程度及哮喘潛伏期的影響。實驗結束后，24 h內處死大鼠，取材，測定并比較支氣管壁厚度、氣道上皮下膠原沉積程度;測定血中HMGB1濃度;免疫組織化學測定支氣管平滑肌中α-SMA和氣道組織TLR4的蛋白表達;RT-PCR法測定肺組織HMGB1 mRNA表達變化。結果：黃芩苷可明顯改善病鼠的哮喘程度，延長哮喘潛伏期（P<0.05～0.01）;可有效減輕病鼠支氣管管壁增厚及氣道上皮下膠原沉積程度（P<0.05）;明顯降低血漿中HMGB1的含量，肺組織中的HMGB1 mRNA表達呈下降趨勢，但差異無統計學意義（P>0.05）;可明顯降低氣道組織中的TLR4，氣管平滑肌中α-SMA的蛋白表達及TLR4 mRNA的表達水平（P>0.05）。結論：黃芩苷具有抗哮喘作用，其作用可能與其影響HMGB1/TLR4通路的信號傳導相關。

關鍵詞 黃芩苷;哮喘;地塞米松;哮喘潛伏期;傳導通路;大鼠

Abstract Objective：To study the effects of Baicalin on prevention and treatment of bronchial asthma and its possible mechanism.Methods：A total of 54 SD rats were randomly divided into a normall group，an asthma model group，a dexamethasone group，baicalin high and low dose groups by weight.Animal model of bronchial asthma was induced by ovalbumin （OVA）.The corresponding drugs were given by orally intragastric administration once a day for 4 weeks.The normal group and the asthma model group were replaced by same volume of normal saline （NS）.The effects on asthmatic degree and the latent period of asthma of each rats group were observed after treatment.After the experiment，the rats were killed within 24 h for collection of materials.The thickness of bronchial wall，the degree of collagen deposition in airway，the concentration of HMGB1 in blood，the expression of α-SMA in bronchial smooth muscle and TLR4 in airway were measured by immunohistochemistry.The expression of HMGB1 mRNA in lung tissue was determined by RT-PCR method.Results：Baicalin high and low dose groups could obviously improve the asthmatic degree and prolong the latent period of asthma （P<0.05-0.01），and could effectively reduce the thickness of bronchial wall and the degree of subcutaneous collagen deposition in airway （P<0.05）.The content of HMGB1 in plasma was significantly decreased，and the expression of HMGB1 mRNA in lung tissue was decreased，but there was no significant difference （P>0.05）.The protein expression of α-SMA and TLR4，the expression of TLR4 mRNA in tracheal smooth muscle were significantly decreased （P>0.05）.Conclusion：Baicalin has an effect of anti-asthmatic，which may be related to its influence on signal transduction of the HMGB1/TLR4 pathway.

Key Words Baicalin;Asthma;Dexamethasone;Asthma latency;Conduction pathway;Rat

中圖分類號：R285.5文獻標識碼：Adoi：10.3969/j.issn.1673-7202.2019.06.012

黃芩苷（Baicalin）是植物黃芩的主要有效成分之一，具有清熱解毒、抗炎、抗變態反應等多方面的藥理作用[1]。近年來隨著國內外對黃芩苷研究的不斷深入，其越來越多的作用如抗氧化、免疫調節、促細胞凋亡等多作用被發現。高遷移族蛋白B1（High Mobility Group Box 1，HMGB1）是一種高度保守的核蛋白，為重要的內源性炎性反應遞質，既是早期炎性反應的觸發因子，又是晚期炎性反應的啟動因子[2]。……