迷走神经切断和NK3受体拮抗剂干预在辣椒素诱导小鼠咳嗽中的作用

目的:观察右侧迷走神经切断及NK3受体拮抗剂对辣椒素诱导小鼠咳嗽的作用及其机制。方法:将48只小鼠随机分为4组,分别为:右侧迷走神经切断术组、右侧假手术组、SR 142801腹腔注射组和生理盐水对照组。辣椒素雾化制作小鼠咳嗽模型后,分别进行迷走神经切断术、假手术、SR142801腹腔注射及生理盐水腹腔注射,SR142801组及生理盐水对照组腹腔注射每日1次,连续7天。第8天计数各组所有小鼠咳嗽次数,检测所有小鼠肺组织中SP(substance P,P物质)、NKA(neurokinin A,神经肽A)、NKB(neurokinin B,神经肽B)表达水平。结果:右侧迷走神经切断组术后咳嗽次数(6.92±1.78)次]较术前(7.83±2.48)次]显著降低(P0.01),较假手术组(7.58±2.43)次]降低(P0.05)。右侧迷走神经切断组术后SP、NKA、NKB水平较对照组显著降低(P0.05),SR 142810组干预后咳嗽次数(8.67±1.37)次]较干预前(8.33±2.15)次]无明显降低(P0.05)。SR 142801组腹腔注射后NKB(8.32±0.86)pg/m L]较生理盐水对照组(8.83±0.80)pg/m L]无明显降低(P0.05)。结论:迷走神经切断可以抑制辣椒素诱导的咳嗽,其机制主要与减少迷走神经相关神经肽SP、NKA、NKB的表达有关,而NK3受体拮抗剂SR142801对辣椒素诱导的咳嗽无明显抑制作用。

Role of Vagotomy and NK3 Receptor Antagonist Intervention in Capsaicin -Induced Cough in Mice

ABSTRACT Objective: To observe the effectiveness and mechanism of right vagotomy and NK3 receptor antagonist on capsaicin-induced cough in mice. Methods: 48 mice were randomly divided into 4 groups: the right vagotomy group (hereinafter referred to as RV group), the right sham operation group (hereinafter referred to as RS group), the SR 142801 group (hereinafter referred to as SR group) and the normal saline control group (hereinafter referred to as NS group). Capsaicin atomization was used to produce cough models in each group respectively. Then, vagotomy, sham operation, SR142801 intraperitoneal injection and normal saline intraperitoneal injection were performed; mice in SR142801 group and normal saline control group were injected once per day for 7 days. The coughing times of all mice were counted on the eighth day. The expression levels of SP (substance P), NKA (neurokinin A) and NKB (neurokinin B) in all mice lungs were detected. Results: The coughing times post operation in RV group(6.92±1.78) times] decreased compared with those (7.83±2.48)times ] preoperative (P<0.01), and significantly decreased than that in the sham operation group (7.58 ± 2.43) times] (P<0.05). SP, NKA and NKB in the right vagotomy group decreased significantly rather than those in control group (P<0.05). The frequency of coughing after SR 142810 intraperitoneal (8.67±1.37) times] had no significant difference compared with previous intraperitoneal (8.33±2.15) times] (P>0.05). Compared with that of the NS group(8.83±0.80) pg/mL], the NKB of SR 142801 group(8.32±0.86) pg/mL] had no significant difference (P>0.05). Conclusion: Vagotomy could inhibit capsaicin-induced cough, and its mechanism was mainly related to the decrease of the expression of neuropeptide SP, NKA and NKB which was related to vagal nerve. The NK3 receptor antagonist SR142801 had no obvious inhibitory effect on capsaicin-induced cough.