七氟烷是儿科麻醉的主要用药，其诱发气道平滑肌痉挛/舒张的“双相”作用已成为研究热点。既往报道和我们前期研究发现，七氟烷在“发育期气道”中更倾向为痉挛作用，诱发新生儿严重气道高反应性（AHR）发生，但机制不明，亟待研究。我们进一步预实验发现香草酸瞬时受体1 (TRPV1)通道蛋白激活可能是七氟烷致发育期气道AHR进程中的关键事件，具备防治靶点设计及临床转化价值。鉴于此，本项目拟构建新生大鼠AHR模型、TRPV1基因敲除小鼠模型及气道平滑肌细胞离体培养模型；利用通道活性上调/下调、蛋白活化检测、细胞生物力学及气道力学等生物学技术，研究发育期气道暴露于七氟烷时AHR的发生发展与TRPV1通路及其下游重要基因/蛋白表达/活化变化的相关性；增进对发育期气道AHR机制的认识，以期阐明TRPV1-NKA/NKB通路在七氟烷致发育期大鼠AHR中的作用机制；从而探寻一条临床防治的新途径并奠定一定的理论基础。

Sevoflurane is a major agent in pediatric anesthesia. Bidirectional effects on airway smooth muscles, namely spasm and relaxation of airway smooth muscles, induced by sevoflurane have become a hot research topic. Previous reports and previous research found that sevoflurane tended to play a spasm role in airway at development phase. It can induce the occurrence of neonatal severe airway hyperresponsiveness (AHR), but the mechanism is unknown and needs to be studied. We found in further pre-experiment that activation of proteins of transient receptor potential vanilloid -1 (TRPV1) pathway might be a key event in the process during which sevoflurane induced AHR, which is worth of design of target for prevention and treatment and clinical transformation. Considering this, this project intends to construct AHR model in neonatal rats, TRPV1 gene knock-out mice model and in vitro culture model of airway smooth muscle cells; using biological technologies including up-regulation/down-regulation of channel activity, detection on protein activation, cell biomechanics and airway mechanics, this study studied the correlations between the occurrence and development of AHR with the changes of expressions and activities of TRPV1 pathway and its important downstream genes and proteins when the airway at development phase was exposed to sevoflurane, to enhance the understanding on the mechanism of AHR at development phase and clarify the mechanism of TRPV1-NKA/NKB pathway on rats with AHR at development phase induced by sevoflurane, so as to provide a certain theoretical basis for finding a new way for clinical prevention and treatment.