若干中药组分对哮喘小鼠气道重建的影响与机制研究

发布时间：2018-03-29 08:52

本文选题：中药组分　切入点：气道重建　出处：《复旦大学》2012年博士论文

【摘要】：目的：基于病理形态和肺功能的检测,并利用免疫组化、Western bloting等技术检测哮喘气道重建发生过程中的关键细胞因子,通过对哮喘气道重建模型小鼠灌服若干中药组分,观察其对哮喘气道重建模型小鼠的影响,并与相关现代药物做对照；体外培养小鼠气道平滑肌细胞,利用相关技术检验若干中药组分对气道平滑肌细胞周期的影响。从而验证若干中药组分对哮喘气道重建的防治作用,初步探索中药组分防治气道重建的机制,为哮喘气道重建的防治提供一个新的干预方法和研究思路。方法：采用腹腔注射致敏液及连续雾化吸入1%卵蛋白的方法复制小鼠哮喘气道重建模型,体外培养小鼠气道平滑肌细胞。利用免疫组化、Western bloting等技术,探索若干中药组分对哮喘气道重建模型的影响及其作用机制。结果：1.若干中药组分对小鼠肺功能的影响：一定剂量的黄芩苷和淫羊藿苷对哮喘气道重建模型小鼠Penh值的升高有明显的抑制作用,从而改善肺功能。糖皮质激素地塞米松在这一方面能产生相同的效应。中药组分黄芪甲苷和生地梓醇不能改善气道重建模型小鼠的肺功能。2.若干中药组分对小鼠哮喘气道重建模型肺组织形态的影响：一定剂量的黄芩苷和淫羊藿苷能明显抑制哮喘气道重建小鼠支气管管腔狭窄,支气管平滑肌肌层的增厚和细胞的增生,从而缓解了气道重建的程度。但中药组分黄芪甲苷、生地梓醇和地塞米松却没有这样的作用。3.若干中药组分对多个细胞因子的影响：一定剂量的黄芩苷和淫羊藿苷能减少哮喘气道重建模型小鼠肺组织中TGF-β1和VEGF的表达；能降低模型小鼠血清和肺泡灌洗液中IL-13表达水平,另外黄芩苷还能降低ET-1表达。这可能是黄芩苷和淫羊藿苷防治哮喘气道重建的重要机理。4.若干中药组分对气道平滑肌增殖的影响：一定浓度的黄芩苷和淫羊藿苷通过影响ERK、p21ras和cyclinD1的表达来抑制气道平滑肌增殖,但抑制程度比地塞米松低。5.中药组分淫羊藿苷、黄芪甲苷和生地梓醇联合应用能缓解哮喘气道重建模型小鼠Penh值的升高,但未能找到其发挥作用的关键细胞因子。中药组分复方对气道重建模型小鼠气道璧增厚的情况没有明显改善。提示中药组分联合应用有一定的协同作用,但其作用远未达到预期效果,中药组分复方的配伍需要进一步的深入探讨。结论：一定剂量的黄芩苷和淫羊藿苷能缓解哮喘气道重建；其具体机制与黄芩苷和淫羊藿苷能够调节哮喘气道重建发生过程中的关键细胞因子相关。
[Abstract]:Objective : To detect the key cytokines in the airway remodeling of asthma based on the detection of pathological morphology and lung function , and to observe the effects of several traditional Chinese medicinal components on the airway remodeling model mice by using immunohistochemistry , Western bloting and so on .
The effect of several traditional Chinese medicine components on airway smooth muscle cell cycle of airway smooth muscle cells was studied by means of correlation technique .

Methods : The model of airway remodeling in mice was replicated by intraperitoneal injection of sensitizing liquid and continuous atomization of 1 % egg protein . The effects of several traditional Chinese medicine components on airway remodeling model of asthma were investigated by immunohistochemistry and Western bloting .

Results : 1 . The effects of several traditional Chinese medicine components on the lung function of mice were studied .
The expression of IL - 13 in the serum and alveolar lavage fluid of model mice can be reduced , and baicalin can decrease the expression of ET - 1 . This may be an important mechanism for the prevention and treatment of airway smooth muscle by baicalin and epimedin .

Conclusion : A dose of baicalin and epimedin can alleviate airway remodeling in asthma .
Its specific mechanism is related to baicalin and epimedin to regulate the key cytokine in the course of airway remodeling in asthma .

【学位授予单位】：复旦大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R562.25

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