主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2019, Vol. 42 ›› Issue (1): 37-43.doi: 10.3969/j.issn.1006-2157.2019.01.007

• 中药药理 • 上一篇    下一篇

麦门冬汤对肺纤维化大鼠肺功能及内质网应激作用的影响

申萌萌1, 南亚楠1, 唐磊2, 田如玉3, 朱曼4, 康荻5, 张瑞颖6, 牛建昭7, 李亚东1#   

  1. 1 北京中医药大学生命科学学院 北京 100029;
    2 北京市朝阳区第三医院;
    3 华北理工大学理学院;
    4 淄博市中西医结合医院;
    5 华据医疗评估信息技术(北京)有限公司;
    6 北京101中学;
    7 北京中医药大学中医学院
  • 收稿日期:2019-06-12 出版日期:2019-01-30 发布日期:2019-03-01
  • 通讯作者: 李亚东,男,博士,副教授,硕士生导师,研究方向:中医药防治肺纤维化的系统生物学研究,E-mail:lydtry@sina.com
  • 作者简介:申萌萌,女,在读硕士生
  • 基金资助:
    国家自然科学基金资助项目(No.81202787、No.81573716),高等学校学科创新引智计划(No.b07007)

Influence of Maimendong Tang on lung function and endoplasmic reticulum stress in rats with pulmonary fibrosis

Shen Mengmeng1, Nan Yanan1, Tang Lei2, Tian Ruyu3, Zhu Man4, Kang Di5, Zhang Ruiying6, Niu Jianzhao7, Li Yadong1#   

  1. 1 School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China;
    2 Third Hospital of Beijing Chaoyang District, Beijing 100121, China;
    3 School of Science, North China University of Science and Technology, Hebei 063000, China;
    4 Zibo Hospital of Integrated Chinese and Western Medicine, Shandong 255000, China;
    5 Huaju Healthcare Assessment Information Technology (Beijing) Co., Ltd, Beijing 100102, China;
    6 Beijing 101 Middle School, Beijing 100091, China;
    7 School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
  • Received:2019-06-12 Online:2019-01-30 Published:2019-03-01
  • Contact: Li Yadong, male, PhD., Associated Professor, Master’s Supervisor. Research direction: systematic biology study on prevention and treatment of lung fibrosis with Chinese medicine. E-mail: lydtry@sina.com
  • Supported by:
    National Natural Science Foundation of China(No.81202787,No.81573716), Supported by the 111 Project(No.b07007)

摘要: 目的 探讨麦门冬汤改善博来霉素所致肺纤维化模型大鼠肺功能及内质网应激(ERS)作用的相关机制。方法 健康雄性SD大鼠随机分为正常组、模型组、麦门冬汤1组(麦门冬与大枣质量比4∶1)、麦门冬汤2组(麦门冬与大枣质量比20∶1),经气管插管雾化注射博来霉素建立肺纤维化大鼠模型。造模后第14天每日早晚2次灌胃麦门冬汤,连续给药20 d。观察大鼠一般情况,通过HE和Masson染色观察肺组织的病理变化,检测大鼠用力肺活量(FVC)、0.4秒率(FEV0.4/FVC)、质量FVC、吸气阻力(Ri)、呼气阻力(Re)、肺顺应性(Cydn),并用Western blot和免疫组织化学染色分析肺组织中葡萄糖调节蛋白78(GRP78)和C/EBP同源蛋白(CHOP)的表达情况。结果 与正常组相比,模型组FVC降低、0.4秒率升高、质量FVC下降、Cydn降低;与模型组相比,麦门冬汤1组和麦门冬汤2组FVC升高、0.4秒率降低,麦门冬汤2组质量FVC回升,麦门冬汤1组和麦门冬汤2组Cydn升高。病理可见模型组大鼠的肺组织实变区内慢性炎性细胞浸润,大量胶原沉积,高表达的GRP78和CHOP蛋白主要定位于空泡化的Ⅱ型肺泡上皮细胞(AECⅡs)。麦门冬汤2组大鼠炎症缓解,胶原沉积减少,肺组织中GRP78和CHOP蛋白的表达均减少。结论 麦门冬汤能够明显改善大鼠肺功能,减少肺间质胶原沉积,可能与调节纤维化肺组织实变区内AECⅡs的GRP78和CHOP蛋白表达,缓解ERS压力,恢复AECⅡs的正常功能有关。

关键词: 麦门冬汤, 内质网应激, Ⅱ型肺泡上皮细胞, 葡萄糖调节蛋白78, C/EBP同源蛋白, 大鼠

Abstract: Objective To investigate the relative mechanism of Maimendong Tang (Ophiopogon Decoction) in amelioration of lung function and endoplasmic reticulum stress (ERS) in rats with bleomycin-induced pulmonary fibrosis. Methods Male healthy SD rats were randomly divided into normal group, model group, Maimendong Tang group 1 and Maimendong Tang group 2. The rat model of pulmonary fibrosis was established by bleomycin pulverization via tracheal intubation. On the 14th d after modeling, Maimendong Tang was intragastrically given to Maimendong Tang group 1 and Maimendong Tang group 2 twice a day for 20 d continuously. The general conditions were observed, and pathological changes of lung tissue were observed after HE and Masson staining. The forced vital capacity (FVC), 0.4 second rate (FEV 0.4/FVC), mass FVC, inspiratory resistance (Ri), expiratory resistance (Re) and dynamic pulmonary compliance (Cydn) were detected by using spirometer. The expressions of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) protein in lung tissue were analyzed by using Western blotting assay and immunohistochemistry staining technique. Results Compared with normal group, FVC, FVC/lung mass and Cydn decreased, and 0.4 second rate increased in model group. Compared with model group, FVC increased and 0.4 second rate decreased and Cydn increased in Maimendong Tang group 1 and Maimendong Tang group 2, and mass FVC increased in Maimendong Tang group 2. Pathological sections showed that there were chronic inflammatory cell infiltration in consolidation zone of lung tissue and massive collagen deposition, GRP78 and CHOP with high expressions were mainly positioned in vesicular type II alveolar epithelial cells (AECIIs). The inflammation was relieved, collagen deposition was decreased, protein expressions of GRP78 and CHOP were reduced and in Maimendong Tang group 2. Conclusion Maimendong Tang can significantly improve lung function and reduce lung interstitial collagen deposition, which may be related to regulation of protein expressions of GRP78 and CHOP in AECIIs in consolidation zone of lung tissue, relief of ERS, and recovery of normal AECIIs function.

Key words: Maimendong Tang (Ophiopogon Decoction), endoplasmic reticulum stress, type II alveolar epithelial cells, glucose regulated protein 78, C/EBP homologous protein, rats

中图分类号: 

  • R285.5