芦竹碱对哮喘小鼠气道炎症和重塑的保护作用及机制  

Protective effect of gramine on airway inflammation and remodeling in asthmatic mice and its mechanism

作　　者：李雅琼 黄静 LI Ya-qiong;HUANG Jing(Clinical Competence Training Center,Sanquan College,Xinxiang Medical University,Xinxiang Medical University,Xinxiang Henan 453000,China;Dept of Internal Medicine,Sanquan College,Xinxiang Medical University,Xinxiang Henan 453000,China)

机构地区：[1]新乡医学院三全学院临床能力培训中心,河南新乡453000 [2]新乡医学院三全学院内科学教研室,河南新乡453000

出　　处：《中国药理学通报》2025年第4期718-725,共8页Chinese Pharmacological Bulletin

基　　金：河南省科学技术厅公益性技术应用研究项目(No.CK202208156072351);新乡医学院三全学院骨干教师培养计划(SQ2025GGJS03)。

摘　　要：目的探讨芦竹碱对哮喘模型小鼠的气道炎症和重塑的治疗作用及潜在的机制。方法通过卵清蛋白(ovalbumin,OVA)敏感的BALB/c雌性小鼠建立哮喘模型,随后进行芦竹碱干预(25、100 mg·kg^(-1))。通过HE、PAS及Masson染色的肺切片评估芦竹碱对哮喘小鼠肺组织形态学的改善效果。对支气管肺泡灌洗液(BALF)中炎性细胞数目计数,并用ELISA法检测BALF中白介素(IL)-4、IL-5、IL-6、IL-13和肿瘤坏死因子(TNF-α)水平。利用免疫组化和免疫印迹检测肺组织中α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(COL-Ⅰ)及脑源性神经营养因子(BDNF)/酪氨酸激酶B(TrkB)信号蛋白的表达。用BDNF/TrkB激动剂干预后,通过肺组织病理学检验和BALF中炎性细胞数目计数验证芦竹碱对哮喘的治疗作用是否与BDNF/TrkB信号通路有关。结果芦竹碱明显降低了OVA诱导的小鼠气道炎症细胞浸润及BALF中促炎因子的水平(P<0.01),同时减轻了气道重塑(P<0.01),并抑制肺组织中α-SMA和COL-Ⅰ的表达(P<0.01)。芦竹碱能抑制哮喘小鼠BDNF/TrkB信号通路的活性,而BDNF/TrkB激动剂则能部分逆转芦竹碱的抗哮喘功能(P<0.01)。结论芦竹碱对OVA诱导的哮喘小鼠气道炎症和重塑表现出改善作用,该作用与其抑制BDNF/TrkB信号通路有关。Aim To investigate the therapeutic effects of gramine on airway inflammation and remodeling in a mouse model of asthma and to explore the potential mechanisms.Methods Female BALB/c mice sensitized with ovalbumin(OVA)were used to establish an asthma model,followed by gramine intervention(25,100 mg·kg^(-1)).The improvement of lung tissue morphology in asthmatic mice by gramine was evaluated by HE,PAS,and Masson staining of lung tissue sections.The number of inflammatory cells in bronchoalveolar lavage fluid(BALF)was counted,and the levels ofIL-4,IL-5,IL-6,IL-13,and TNF-αin BALF were detected by ELISA.The expressions ofα-smooth muscle actin(α-SMA),type I collagen(COL-Ⅰ),and BDNF/TrkB signaling proteins in lung tissue were detected by immunohistochemistry and Western blot.Following the intervention with BDNF/TrkB agonists,the therapeutic efficacy of gramine in asthma was assessed through histopathological analysis of lung tissue and quantification of inflammatory cell counts in BALF to determine its association with the BDNF/TrkB signaling pathway.Results Gramine significantly reduced the inflammatory cell infiltration and pro-inflammatory factor levels in the bronchial airway of mice induced by OVA(P<0.01),while alleviating airway remodeling(P<0.01)and inhibiting the expression ofα-SMA and COL-Ⅰin lung tissue(P<0.01).Gramine could inhibit the activity of the BDNF/TrkB signaling pathway in asthma mice,while the BDNF/TrkB agonist could partially reverse the anti-asthmatic function of gramine(P<0.01).Conclusion Gramine exhibits significant improvement in airway inflammation and remodeling in OVA-induced asthmatic mice,which is related to its inhibition of the BDNF/TrkB signaling pathway.

关 键 词：芦竹碱 哮喘 小鼠 气道炎症 气道重塑 BDNF/TrkB信号通路 

分 类 号：R-332[医药卫生] R284.1R322.33R562.11R562.25