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目的:探讨中药验方天龙喘咳灵水煎剂干预支气管哮喘气道重塑的可能机制。方法:实验设3组,盐水对照组,哮喘模型组,天龙咳喘灵治疗组。小鼠经常规OVA致敏后连续18天给予1.5%的OVA雾化吸入激发。治疗组小鼠每次激发后给予雾化天龙咳喘灵水煎剂。末次激发后72h,利用气道插管检测各组小鼠气道反应性;肺泡灌洗,观察肺泡灌洗液(BALF)中细胞总数和细胞分类;分离小鼠右肺制备组织切片进行病理分析;分离小鼠左肺提取总蛋白,检测肺部α-SMA表达水平和丝裂原活化蛋白激酶(mitogen activatedprotein,MAPK)信号通路,信号传导及转录活化因子-3(signal transducers and activators of transcription-3,Stat3)的活化情况。结果:与盐水对照组相比,OVA-哮喘组小鼠气道反应性显著升高(P<0.01),相应BALF中细胞总数和嗜酸性粒细胞比例也明显增加(P<0.01);天龙咳喘灵治疗组小鼠气道反应性明显低于哮喘组小鼠(P<0.01),但BALF中细胞总数和嗜酸性粒细胞比例亦较正常对照组增加(P<0.01)。肺组织病理切片显示哮喘组上皮下基底膜层明显增厚,α-SMA表达水平增高,而天龙咳喘灵治疗组气道上皮下未见明显改变,α-SMA表达水平与盐水对照组无显著差别。在哮喘小鼠肺部,MAPKs信号通路当中的胞外信号调节激酶(extracellular signal-reg-ulated kinase,ERK)通路和Stat3通路明显激活,而天龙咳喘灵能有效抑制该信号途径的活化。结论:天龙喘咳灵水煎剂能有效防治慢性哮喘小鼠模型的气道重塑,其机制可能是通过抑制ERKs通路和Stat3通路的活化实现的。
Objective: To investigate the possible mechanism of traditional Chinese medicine Tianlongchuanling decoction on bronchial asthma airway remodeling. Methods: The experimental group 3, saline control group, asthma model group, Tianlongkechuanling treatment group. Mice were challenged with 1.5% OVA aerosol inhalation for 18 consecutive days after conventional OVA sensitization. The mice in treatment group were given nebulized Tianlongkechuanling decoction after each challenge. 72h after the last challenge, airway intubation was used to detect airway responsiveness in each group of mice; alveolar lavage was performed to observe the total number of cells and cell classification in BALF; histopathological analysis was performed on the right lung of mice The total protein was extracted from the left lung of the mice and the expression of α-SMA and the signal transducers and activators of transcription-3 (MAPK) 3, Stat3) activation. Results: Compared with the saline control group, the airway responsiveness in OVA-asthmatic mice was significantly increased (P <0.01), and the total number of cells and eosinophil proportion in the corresponding BALF were also significantly increased (P <0.01) The airway responsiveness in the asthma group was significantly lower than that in the asthma group (P <0.01), but the total cell number and eosinophil percentage in the BALF were also increased (P <0.01). Pulmonary histopathology showed that the subepithelial basement membrane layer of asthma group was significantly thicker and the expression of α-SMA was increased, while there was no significant change in the airway epithelium of Tianlong Kechuanling treatment group, and there was no significant difference in α-SMA expression between the asthma group and saline control group . In the lungs of asthmatic mice, extracellular signal-reg-ulated kinase (ERK) pathway and Stat3 pathway were significantly activated in the MAPKs signaling pathway, and Tianlong Kechuanling could effectively inhibit the activation of this signaling pathway. Conclusion: Tianlongchuanling decoction can effectively prevent and cure airway remodeling in chronic asthmatic mice model by inhibiting the activation of ERKs pathway and Stat3 pathway.