基于IL-31—TRPV1轴的蛇床子素抗AD慢性瘙痒作用机制研究

IL-31- TRPV1 plays an important role in the chronic pruritus of atopic dermatitis (AD). IL-31 induces itch may including both direct and indirect pathways. IL-31 directly activates IL-31 receptors and open TRPV1 on nerve fibers to produce scratching. Furthermore, IL-31 activates IL-31 receptors of keratinocyte, which release the itch mediators TXA2 and LTB4. TXA2 and LTB4 can induce scratching by activating the TXA2 receptors and LTB4 receptors and opening TRPV1 on the nerve fibers. TRPV1 is the downstream channel of itch pathway mentioned above. The fruits of Cnidium is a commonly used anti-itch tradtional herb. Previous studies showed that osthole, the main component of Cnidium, inhibited TRPV1 current. However, whether osthole can regulate IL-31-mediated chronic pruritus of AD is unclear. We proposed that osthole can inhibit AD chronic pruritus based on IL-31-TRPV1 axis in AD animal model and keratinocytes model. Behavior test, immunohistochemistry, ELISA, RT-PCR Westen Blot, calcium imaging and electrophysiological methods were used to observe the antipruritic effect of osthole on chronic pruritus. All above study will provide more scientific datas for utilization of osthole for the clinical treatment of chronic itch.

IL-31-TRPV1在特应性皮炎慢性瘙痒中扮演重要的角色。IL-31引起瘙痒包含直接与间接通路。IL-31可直接激活神经末梢上IL-31受体以及TRPV1，产生痒觉。IL-31也可激活角化细胞，释放痒觉介质血栓素A2（TXA2）、白三烯B4（LTB4），TXA2、LTB4激活神经末梢上的受体以及TRPV1，产生痒觉。TRPV1是下游共同的通道。蛇床子是常用止痒民族药材，前期研究表明蛇床子成分蛇床子素（Osthole）抑制TRPV1电流。但是，osthole是否可以调节IL-31介导的慢性瘙痒，尚不清楚。课题组提出“Osthole通过调节IL-31-TRPV1轴相关靶点抗慢性瘙痒”的假说。通过动物与化细胞模型，行为学、ELISA、RT-PCR、western blot、钙成像、电生理等方法，观察Osthole抗慢性瘙痒作用机制。研究将为Osthole临床上治疗慢性瘙痒提供更多的依据。

IL-31，TRPV1在特应性皮炎慢性瘙痒中扮演重要的角色。蛇床子素具有抑制慢性瘙痒的作用，但是它作用机制尚不清楚。研究主要谈探讨蛇床子素通过调节IL-31,TRPV1抑制慢瘙痒的作用机制。只要开展以下研究内容：蛇床子乙酸乙酯提取物抑制特应性皮炎模型小鼠慢性瘙痒。蛇床子素抑制特应性皮炎模型小鼠慢性瘙痒。蛇床子素可通过激活TRPV1导致其脱敏。蛇床子素抑制RBL-2H3释放IL-31。研究发现蛇床子乙酸乙酯提取物以及蛇床子素可以改善特应性皮炎症状，抑制慢性瘙痒以及相关细胞因子。。此外，蛇床子素可以直接激活TRPV1，并且导致其脱敏，从而抑制其瘙痒行为。研究还发现蛇床子素抑制肥大细胞释放组胺，IL-31、IL-6、TNFα、IL-1β,并抑制炎症相关的NF-κB通路。研究将为未来开放蛇床子素相关的止痒药物提供实验依据。