孟鲁司特对幼年哮喘气道重塑大鼠感觉神经肽受体NK1R表达的影响

Effect of montelukast on the expression of neurokinin-1 receptor in young asthmatic rats with airway remodeling

摘要:

目的：探讨孟鲁司特对幼年哮喘气道重塑大鼠中感觉神经肽受体NK1R表达的影响。方法：24只Sprague-Dawley（SD）大鼠随机分为对照组、哮喘组和孟鲁司特组，每组8只。应用卵白蛋白（OVA）雾化吸入法建立哮喘大鼠模型，对照组大鼠应用生理盐水代替致敏液和1%OVA，孟鲁司特组于每次激发前2 h以孟鲁司特（15 mg/kg）灌胃，共持续8 周。采用免疫组化、real-time PCR和Western blot等方法，从mRNA和蛋白水平动态观察NK1R在哮喘大鼠气道重塑中的表达水平及孟鲁司特对其表达的影响。结果：哮喘组NK1R mRNA及蛋白的表达水平均较对照组明显增加，差异有统计学意义(P<0.01)；孟鲁司特干预后NK1R mRNA及蛋白表达水平较哮喘组减少(P<0.05)，但仍高于对照组(P<0.01)。结论哮喘：诱发大鼠气道NK1R的表达增加，孟鲁司特能够下调哮喘大鼠气道重塑中NK1R的表达水平。

Abstract:

OBJECTIVE: To investigate the effect of montelukast on the expression of sensory neuropeptide (neurokinin-1) receptor (NK1R) in young asthmatic rats with airway remodeling. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into control group (n=8), asthma (n=8), and montelukast groups (n=8). A rat model of asthma was induced by ovalbumin (OVA) inhalation. Normal saline was used instead of sensitizing solution and 1% OVA in the control group. Each rat in the montelukast group was given montelukast (15 mg/kg) by gavage 2 h before OVA inhalation. All rats received their respective treatments for 8 weeks. Immunohistochemistry, real-time PCR and Western blot were used to measure the mRNA and protein expression levels of NK1R in asthmatic airway remolding and to evaluate the effect of montelukast on NK1R expression. RESULTS: The asthma group showed significantly higher mRNA and protein expression levels of NK1R than the control group (P<0.01). The mRNA and protein expression levels of NK1R in the montelukast group were significantly lower than in the asthma group (P<0.05), but significantly higher than in the control group (P<0.01). CONCLUSIONS: Rats with induced asthma have upregulated NK1R expression in the airway, and montelukast can downregulate NK1R expression during airway remodeling.