麦门冬汤及其组分治疗肺部纤维化的物质基础和药效学研究

Study on the material basis and pharmacodynamic effects of Maimendong Decoction and its fractionated components in the treatment of pulmonary fibrosis

关键词:  麦门冬汤  肺部纤维化  物质基础  抗炎  氧化应激  胶原

Key words:  Maimendong Decoction  pulmonary fibrosis  material base  anti-inflammatory  oxidative stress  collagen

摘要:

[目的] 研究麦门冬汤及其组分的物质基础并探讨其在治疗肺纤维化（PF）中的药效作用。[方法] 应用中药提取和色谱分离技术，获得麦门冬汤总提物及其不同极性组分并采用液质联用技术进行定性分析。采用气管注射博来硫酸霉素复制SD大鼠肺纤维化模型。将所有大鼠随机分为空白组（C组）、模型组（M组）、麦门冬汤总提物给药组（Z组）、麦门冬汤水洗脱组分给药组（W组）、麦门冬汤50%乙醇洗脱组分给药组（E50组）、麦门冬汤95%乙醇洗脱组分给药组（E95组）。造模结束后，每只大鼠的灌胃给药剂量均为29.16 g/（kg·d）原药材，空白组和模型组给予灌胃等量的生理盐水，连续灌胃14 d后测定大鼠血清中超氧化物歧化酶（SOD）、丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）、白细胞介素10（IL-10）以及肺组织中羟脯氨酸（Hyp）、Ⅰ型胶原（COL Ⅰ）、Ⅲ型胶原（COL Ⅲ）的含量；苏木精-伊红（HE）染色观察肺内炎症表现；马松（Masson）染色观察肺内胶原活性。[结果] 从麦门冬汤总提物（Z组分）、W组分、E50组分、E95组分中分别鉴定出37、19、25、82个化学成分。麦门冬汤能够明显改善博莱霉素诱导小鼠肺纤维化，对于抗氧化应激，W组分给药组的药效最为明显；各给药组均可有效减少肺组织异常胶原纤维的沉积；对炎症因子的影响，E50组分给药组与E95组分给药组药效更为明显。相比于各极性给药组，Z组药效更为明显。[结论] 在麦门冬汤及其组分中共鉴定了96个化学成分，包括黄酮类、皂苷类、生物碱类、有机酸类以及其他类型的化合物。与模型组比较，麦门冬汤及其各组分给药均可以有效改善组肺组织出血及弹性降低，明显减低肺内炎症程度，氧化应激程度和胶原纤维的沉积。麦门冬汤可以有效治疗肺部纤维化。

Abstract:

[Objective] To investigate the material basis of Maimendong Decoction and its components，and to explore their therapeutic effects on pulmonary fibrosis（PF）. [Method] Standard herbal extraction techniques and chromatographic separation techniques were applied to obtain the total extract of Maimendong Decoction and its different polarity components，followed by qualitative analysis using liquid chromatography-mass spectrometry（LC-MS）. The PF model in SD rats was replicated by intratracheal injection of bleomycin. All rats were randomly divided into blank group，model group，Z group，W group，E50 group and E95 group. After modeling，each rat received 29.16 g/（kg·d） of crude drug equivalents via intragastric administration，and the blank group and the model group were given the same amount of normal saline. After continuous intragastric administration for 14 days，serum levels of SOD，MDA，TNF-α，IL-10 and and lung tissue levels of Hyp，COL I，COL Ⅲ were measured. Hematoxylin-eosin（HE） staining was used to observe the inflammatory manifestations in the lungs. Masson’s trichrome staining was used to observe the collagen activity in the lungs. [Results] A total of 37，19，25，82 chemical components were identified from the total extract of Maimendong Decoction（Z），W，E50 and E95，respectively. Maimendong Decoction significantly improved bleomycin-induced PF in mice. The W group showed the most significant anti-oxidative stress effects. Each administration group can effectively reduce the deposition of abnormal collagen fibers in lung tissue. The effect of E50 component administration group and E95 component administration group on inflammatory factors was more obvious. Compared with each polar administration group，the efficacy of group Z was more obvious. [Conclusion] A total of 96 chemical components were identified in the total extract and its components of Maimendong Decoction，including flavonoids，saponins，alkaloids，organic acids and other types of compounds. Compared with the model group，Maimendong Decoction and its components can effectively improve the bleeding and elasticity of lung tissue in the group，significantly reduce the degree of inflammation in the lung，the degree of oxidative stress and the deposition of collagen fibers. Maimendong Decoction can effectively treat PF.