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基于TAS2Rs/ROCK通路探究苦味中药黄芩抑制气道刚度防治哮喘的机制研究

批准号:
82104510
项目类别:
青年科学基金项目(C类)
资助金额:
30.0 万元
负责人:
董守金
依托单位:
学科分类:
中药消化与呼吸药理
结题年份:
2024
批准年份:
2021
项目状态:
已结题
项目参与者:
董守金

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中文摘要
深吸气(DI)是一种内在有效阻止气道痉挛的方法,哮喘患者却DI失能,目前尚无DI复能的治疗方法。苦味中药黄芩通过G蛋白偶联受体(GPCRs)的亚型--苦味受体(TAS2Rs)发挥扩张支气管及抗炎作用,但具体作用机制不明。研究证实DI失能与气道刚度增加有关。我们研究发现GPCRs/ROCK通路是调控哮喘气道刚度的重要通路,因此推测“黄芩阻断TAS2Rs/ROCK通路抑制气道刚度使哮喘DI复能”。本研究拟运用大鼠过敏性哮喘模型,利用肺功能仪检测气道阻力水平,构建力-位移检测设备与伺服步进电机系统测定气道力及位移变化,使用ELISA及HE染色测定炎症水平,及Western Blot法检测TAS2Rs/ROCK通路蛋白的表达水平,确证黄芩改善DI失能的药理效应,重点考察黄芩对哮喘气道主动刚度与被动刚度的抑制作用以及与TAS2Rs/ROCK通路的关联性,以期为黄芩DI复能的临床适应症提供研究证据。
英文摘要
Deep inhalation (DI) is an inherently effective way to prevent airway spasms, but asthmatic patients are absent. Our previous studies have found that DI disability in asthma is related to increased airway stiffness, airway inflammation increases active stiffness, mechanical strain offsets passive stiffness, and a ROCK-dependent recovery process. ROCK is highly expressed in asthma. G-protein-coupled receptors (GPCRs)/ROCK pathway is an essential pathway in asthma. Based on this, it is speculated that if the GPCRs/ROCK pathway is effectively blocked, the airway wall's stiffness can be effectively reduced, and asthma DI can be restored. Based on the theory of TCM " nourishing-purging based on visceral conditions." However, the bitter traditional Chinese medicine Scutellaria baicalensis Georgi can exert anti-inflammatory and airway expansion effects through the GPCRs subtype bitter receptor TAS2Rs; its specific mechanism has not been studied. This study intends to use a rat model of allergic asthma to confirm the pharmacological effects of Scutellaria baicalensis Georgi in improving DI disability. Based on this basis, focus on the inhibitory effect of Scutellaria baicalensis Georgi on the active and passive stiffness of asthmatic airway and its association with TAS2Rs/ROCK pathway to provide research evidence for the clinical indications of Scutellaria baicalensis DI rejuvenation.
深吸气(DI)是一种内在有效阻止气道痉挛的方法,哮喘患者却DI失能,目前尚无DI复能的治疗方法。本研究运用大鼠过敏性哮喘模型,使用肺功能仪了解气道阻力水平,力-位移检测设备与伺服步进电机系统测定力及位移变化,Western Blot检测ROCK通路蛋白的表达水平,证实黄芩可以部分缓解哮喘大鼠的DI失能状态,阐明黄芩对哮喘大鼠炎症水平、ASM主动刚度的影响及ROCK- NF-κB p65通路的调控机制及阐明黄芩对哮喘大鼠ASM被动刚度的影响及ROCK-MLC20通路的调控机制,本研究结果发现:黄芩可以扩张Ach激发的哮喘气道收缩,并且通过ROCK- NF-κB p65通路抑制IL-6、IL-8及TNF-a等炎症因子的释放、减轻哮喘大鼠的气道壁厚度及降低气道主动刚度,同时通过MLC20通路降低气道被动刚度,结果表明黄芩具有改善DI失能的药理效应,主要是通过黄芩对哮喘气道主动刚度与被动刚度的抑制作用以及与ROCK通路,为黄芩DI复能的临床适应症提供研究证据,从生物力学方面诠释了 “肺苦气上逆,急食苦以泄之” 的理论,为哮喘的防治提供了新的治疗方向。依托本课题,公开发表相关论文6篇,其中SCI6篇,参加国内会议交流3次,其中大会发言1次,壁报交流2次,培养硕士研究生3名,入选人才计划3人次。
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