天津医药

天津医药 ›› 2023, Vol. 51 ›› Issue (9): 943-947.doi: 10.11958/20222063

• 实验研究 • 上一篇    下一篇

汉防己甲素对支气管哮喘小鼠气道重塑的影响及机制探讨

王生成1(), 李琪2,△(), 蔡潇阳1, 唐咏婕1   

  1. 1.儋州市人民医院呼吸内科（邮编571700）
    2.海南医学院第一附属医院呼吸内科
  • 收稿日期:2023-01-16 修回日期:2023-03-16 出版日期:2023-09-15 发布日期:2023-09-13
  • 通讯作者: △E-mail：lqlq198210@sina.com
  • 作者简介:王生成（1984），男，主治医师，主要从事呼吸系统疾病诊治方面研究。E-mail：wangshengcheng927@163.com
  • 基金资助:
    国家自然科学基金资助项目(81860001)

Effect and mechanism of tetrandrine on airway remodeling in bronchial asthma mice

WANG Shengcheng1(), LI Qi2,△(), CAI Xiaoyang1, TANG Yongjie1   

  1. 1. Department of Respiratory Medicine, Danzhou People's Hospital, Danzhou 571700, China
    2. Department of Respiratory Medicine, the First Affiliated Hospital of Hainan Medical College
  • Received:2023-01-16 Revised:2023-03-16 Published:2023-09-15 Online:2023-09-13
  • Contact: △E-mail：lqlq198210@sina.com

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摘要：

目的 探究汉防己甲素对支气管哮喘小鼠气道重塑及高迁移率族蛋白B1（HMGB1）/Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路的影响。方法 构建支气管哮喘小鼠模型，将建模成功的40只小鼠随机分为模型组，汉防己甲素低（20 mg/kg）、高（40 mg/kg）剂量组和地塞米松（10 mg/kg）组，每组10只。另取10只小鼠不建模作为对照组。各组小鼠给予相应干预2周。ELISA法检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-1β水平；苏木素-伊红染色观察肺组织病理学变化并进行肺损伤评分；测定小鼠支气管管壁厚度和支气管平滑肌厚度；荧光定量PCR（qPCR）和蛋白印迹法（Western blot）检测肺组织HMGB1、TLR4、NF-κB mRNA和蛋白表达水平。结果 对照组小鼠肺组织支气管无病理损伤。与对照组相比，模型组小鼠支气管管壁及平滑肌增厚，黏膜上皮增生、皱襞增多，管腔缩小，气管内黏液渗出明显；血清TNF-α、IL-6、IL-1β水平，肺损伤评分，支气管管壁及支气管平滑肌厚度，HMGB1、TLR4、NF-κB mRNA和蛋白表达水平显著升高（P<0.05）。与模型组相比，汉防己甲素低、高剂量组小鼠肺组织病变程度逐渐减轻，血清TNF-α、IL-6、IL-1β水平，肺损伤评分，支气管管壁及支气管平滑肌厚度，HMGB1、TLR4、NF-κB mRNA和蛋白表达水平依次降低（P<0.05）；汉防己甲素高剂量组和地塞米松组小鼠各项指标比较差异均无统计学意义（P>0.05）。结论 汉防己甲素可减轻支气管哮喘小鼠气道重塑程度和炎性因子水平，保护肺组织，其机制可能与抑制HMGB1/TLR4/NF-κB信号通路有关。

关键词: 粉防己碱, 哮喘, 气道重塑, HMGB1蛋白质, Toll样受体4, NF-κB

Abstract:

Objective To investigate the effect of tetrandrine on airway remodeling and high mobility group protein box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway in bronchial asthma mice. Methods A mouse model of bronchial asthma was established, and 40 model mice were randomly divided into the model group, the tetrandrine low dose (20 mg/kg) group, the high dose (40 mg/kg) group and the dexamethasone (10 mg/kg) group, with 10 mice in each group. Another 10 mice without modeling were useed as the control group. Each group was given corresponding intervention for 2 weeks. Serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL-6) and IL-1β were determined by ELISA. Hematoxylin-eosin staining was used to observe lung histopathological changes, and lung injury score was performed. The thickness of bronchial tube wall and bronchial smooth muscle were determined. Expression levels of HMGB1, TLR4, NF-κB mRNA and protein in lung tissue were detected by fluorescence quantitative PCR (qPCR) and Western blot assay. Results No pathological damage was found in bronchus of lung tissue in the control group. Compared with the control group, the bronchial tube wall and smooth muscle of lung tissue in the model group were thickened, mucosal epithelium hyperplasia, and lumen shrank and tracheal mucus exudated significantly. Serum levels of TNF-α, IL-6 and IL-1β, lung injury score, bronchial wall thickness, bronchial smooth muscle thickness, HMGB1, TLR4, NF-κB mRNA and protein expression levels were increased significantly (P<0.05). Compared with the model group, the degree of lung lesions was gradually reduced in the low and high dose tetrandrine groups, and serum levels of TNF-α, IL-6, IL-1β, lung injury scores, bronchial wall and bronchial smooth muscle thickness, HMGB1, TLR4, NF-κB mRNA and protein expression were successively decreased. There were no significant differences in above indexed between the tetrandrine high dose group and the dexamethasone group (P>0.05). Conclusion Tetrandrine can reduce the degree of airway remodeling and the level of inflammatory factors in mice with bronchial asthma, and protect lung tissue, which may be related to the inhibition of HMGB1/TLR4/NF-κB signal pathway.

Key words: tetrandrine, asthma, airway remodeling, HMGB1 protein, Toll-like receptor 4, NF-kappa B

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