麻杏石甘汤对咳嗽变异性哮喘大鼠呼吸道中TRPV1、NK-1R表达的影响

Effect of Maxing Shigan Decoction(麻杏石甘汤)on the Expression of TRPV1 and NK-1R in the Respiratory Tract of Cough Variant Asthma Rats

目的:探究麻杏石甘汤对咳嗽变异性哮喘(CVA)大鼠呼吸道中辣椒素受体(TRPV1)、速激肽受体(NK-1R)表达的影响。方法:大鼠随机分为正常对照组,模型对照组,布地奈德组及麻杏石甘汤高、中、低剂量组,除正常对照组外,其余大鼠通过卵蛋白(OVA)致敏制备咳嗽变异性哮喘大鼠模型;灌胃给药15 d后,观察各组大鼠一般状态;采用辣椒素激发法比较各组大鼠的咳嗽次数,HE染色法观察大鼠肺、支气管病理变化,ELISA法检测大鼠肺组织中降钙素基因相关肽(CGRP)、速激肽(SP)的含量,Western blotting检测大鼠气管中TRPV1蛋白,肺组织中NK-1R的表达。结果:与正常对照组比较,模型对照组大鼠咳嗽次数明显增多,肺组织中神经肽类物质CGRP、SP含量明显升高,气管中TRPV1蛋白及肺组织中NK-1R蛋白表达明显升高(P<0.01)。与模型对照组比较,麻杏石甘汤低、中、高剂量组大鼠肺及支气管组织病理变化明显减轻且咳嗽次数均明显减少(P<0.01);麻杏石甘汤中、高剂量组大鼠肺组织中CGRP、SP含量和气管中TRPV1蛋白表达明显降低(P<0.01或P<0.05);麻杏石甘汤高剂量组大鼠肺组织中NK-1R蛋白表达明显降低(P<0.01)。结论:麻杏石甘汤可能是通过抑制TRPV1的表达,从而抑制感觉神经肽的释放,降低气道敏感性及改善气道炎症等途径来发挥对CVA模型大鼠的治疗作用。

Objective:To explore the effect of Maxing Shigan Decoction on the expression of TRPV1 and NK-1 R in the respiratory tract of rats with cough variant asthma(CVA).Methods:Rats were randomly divided into normal control group,model control group,budesonide group and Maxing Shigan Decoction high,medium and low-dose groups.Except for the normal control group,other rats were sensitized with ovalbumin(OVA)to prepare cough variant asthma rat models.After 15 days of intragastric administration,the general state of rats in each group was observed,the number of coughs in each group was compared by capsaicin provocation method,the pathological changes of rat lung and bronchus were observed by HE staining method.The contents of calcitonin gene-related peptide(CGRP)and tachykinin(SP)in lung tissue were detected by ELISA.The expression of TRPV1 protein in trachea and NK-1 R in lung tissue were detected by Western blotting.Results:Compared with the normal control group,the number of cough,the contents of neuropeptides CGRP and SP in lung tissue,the expression of TRPV1 protein in trachea and NK-1 R protein in lung tissue were significantly increased in the model control group(P<0.01).Compared with the model control group,the pathological changes of the lungs and bronchial tissues of the rats in the Maxing Shigan Decoction low,medium and high-dose group were significantly reduced,and the number of coughs was significantly reduced(P<0.01).The contents of CGRP and SP in the lung tissues and the expression of TRPV1 protein in the trachea of Maxing Shigan Decoction medium and highdose groups were significantly reduced(P<0.01 or P<0.05).The expression of NK-1 R protein in the lung tissue of rats in the Maxing Shigan Decoction high-dose group was significantly reduced(P<0.01).Conclusion:Maxing Shigan Decoction may play a therapeutic effect on CVA model rats by inhibiting the expression of TRPV1,thereby inhibiting the release of sensory neuropeptides,reducing airway sensitivity and improving airway inflammation.