中文摘要
慢性咳嗽是临床中的常见症状，其患病率高、病因诊断困难、治愈率低，已成为临床中亟待解决的问题。近期有关研究显示，病因不明的慢性咳嗽与咳嗽感受器—TRPV1—敏感性增加相关。许多炎症介质可通过激活PKC、PKA等蛋白激酶途径磷酸化TRPV1，致TRPV1敏感性增加。敏感性增加的TRPV1极易被不同刺激所激活，不仅可直接经由咳嗽反射弧引起咳嗽发作，亦可介导产生气道神经源性炎症，即由感觉神经末梢释放的SP、CGRP、NKA等神经肽所介导的炎症反应，加强咳嗽反射。根据以上病因不明慢性咳嗽的可能发病机制，已经考虑将TRPV1敏感化调节通路上游及下游作为新型止咳药物的研究目标。本实验将深入探讨TRPV1在慢性咳嗽中的发病机制，为病因不明慢性咳嗽的诊治提供新策略、理论依据及临床转化应用价值。
英文摘要
Chronic cough is a very common symptom in clinic. Its characteristics of high prevalence, difficult to diagnosis the etiology, and low curative rate, make it become the urgent problem need to be solved in clinic. Recent research shows, this type of unknown etiology chronic cough may be related to TRPV1 hypersensitivity. Multiple inflammatory mediators activate protein kinases, such as PKC and PKA, which phosphorylates TRPV1. Phosphorylation of TRPV1 induces TRPV1 hypersensitivity, thus, TRPV1 can be activated by various stimuli easily, and through cough reflex arc and airway neurogenic inflammation (which is an inflammatory response caused by SP, CGRP, NKA, released by sensory nerve terminals) induce cough attacks. Based on the above possible pathogenesis of unknown etiology chronic cough, TRPV1 has been considered as a target in novel cough medicine research, which acts on primary afferent neurons. This research will in-depth explore the pathogenesis of TRPV1 in chronic cough, and may provide important insights into novel therapeutic strategies, theoretical basis and application values of clinical transformation capability for unknown etiology of chronic cough.
结题摘要
慢性咳嗽是临床中的常见症状，其患病率高、病因诊断困难、治愈率低，已成为临床 中亟待解决的问题。近期有关研究显示，病因不明的慢性咳嗽与咳嗽感受器—TRPV1—敏 感性增加相关。许多炎症介质可通过激活PKC、PKA等蛋白激酶途径磷酸化TRPV1，致TRPV1 敏感性增加。敏感性增加的TRPV1极易被不同刺激所激活，不仅可直接经由咳嗽反射弧引 起咳嗽发作，亦可介导产生气道神经源性炎症，即由感觉神经末梢释放的SP、CGRP、NKA 等神经肽所介导的炎症反应，加强咳嗽反射。根据以上病因不明慢性咳嗽的可能发病机制 ，本研究将TRPV1敏感化调节通路上游及下游作为新型止咳药物的研究目标，深入探讨TRPV1在慢性咳嗽中的发病机制，为病因不明慢性咳嗽的诊治提供新策略、理论依据及临床转化应用价值。 本研究中，B2受体拮抗剂、PKC受体拮抗剂、TRPV1受体拮抗剂可显著抑制缓激肽、缓激肽联合辣椒素的致咳作用。对比生理盐水组，缓激肽可使TRPV1浓度显著升高（P＜0.05），而PKC受体拮抗剂可使TRPV1浓度显著下调（P＜0.05）。对比生理盐水+辣椒素组，缓激肽+辣椒素组PKC浓度亦显著增加（P＜0.05）。以上实验结果表明，缓激肽可通过PKC蛋白激酶途径使TRPV1表达上调，而敏感性增加的 TRPV1 被辣椒素等物质激活后，可进一步激活 PKC，使 PKC 磷酸化 TRPV1 途径形成一个正反馈体系，TRPV1敏感化调节通路上游及下游均可作为新型止咳药物的研究目标。