当归提取物蒿苯内酯激活TRPA1调控血压的分子机制

Transient receptor potential (TRP) is consistent with the theory of traditional Chinese medicine. Take TRP channel as the target of Chinese medicine and study the molecular mechanism of biological effects of traditional Chinese medicine is of great significance on the modernized property of traditional Chinese medicine. It was reported the essential oil components of traditional Chinese medicine Angelica sinensis, namely ligustilide have the effects of vasodilation. Our previous work confirmed that ligustilide has two-way regulating functions on TRPA1 currents, and studies have reported that TRPA1 induced calcium influx, which can activate calcium activated-potassium ion and inward rectifier potassium channel. Therefore, we propose the following hypothesis: ligustilide could regulate potassium ion channel of vascular smooth muscle cell membrane through calcium signaling induced by TRPA1, which plays an important role in blood pressure regulation and other cardiovascular protective effects. To confirm our hypothesis, we propose to investigate the molecular mechanism of TRPA1 in blood pressure regulation activated by ligustilide, using wild type and TRPA1 gene knockout mice (TRPA1-/-) models, from overall and isolated vascular rings and cultured vascular smooth muscle cells levels. Our research will provide the basis for the clinical exploitation of new anti-hypertension drugs and innovation of the theory of herbal medicine.

瞬时受体电位通道(TRP)与中药药性理论相吻合，以TRP通道作为中药作用的靶分子，研究中药发挥生物学效应的分子机制，对中药药性的现代化研究意义重大。研究报道传统中药当归的主要挥发油成分——蒿苯内酯具有舒血管作用，我们的前期工作证实，蒿苯内酯对TRPA1通道电流具有双向调节作用，且研究报道TRPA1引起钙内流可激活钙激活性钾离子通道和内向整流钾离子通道。因此，我们提出以下理论假设：蒿苯内酯通过TRPA1介导的钙信号调节血管平滑肌细胞膜钾离子通道功能，从而发挥降压等心血管保护作用。为证实上述理论假设，我们拟利用野生型和TRPA1基因敲除小鼠(TRPA1-/-)模型，从整体、离体血管环和培养的血管平滑肌细胞水平，探讨蒿苯内酯激活TRPA1调控血压的分子机制，为临床开发新型降压药物及创新中药药性理论提供依据。