三拗汤对OVA诱导哮喘小鼠模型的效应及TRPV2表达的影响

Effect of San′ao Decoction on ovalbum induced asthmatic mice and expression of TRPV2 in lung

探讨三拗汤对卵蛋白(ovalbumin,OVA)诱导哮喘小鼠的效应及对瞬时感受器电位离子通道蛋白V2(transient receptor potential V2,TRPV2)表达的影响,通过复制OVA诱导小鼠哮喘模型,观察三拗汤干预后的气道炎症、气道高反应性、肺组织病理学等的变化,检测肺组织TRPV2 mRNA和蛋白表达、支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中白细胞介素-4(interleukin-4,IL-4)、IL-10、神经生长因子(nerve growth factor,NGF)、前列腺素D2(prostaglandin D2,PGD2)的水平。结果显示,与空白组相比,模型组表现出典型的哮喘表型,外周血及BALF中嗜酸性粒细胞(eosinophils,EOS)水平显著升高(P<0.01),气道高反应性增强(P<0.01),肺组织损伤严重;小鼠肺组织中TRPV2的mRNA和蛋白表达显著上调,BALF中IL-4,IL-10,NGF,PGD2水平显著增加(P<0.05,P<0.01)。与模型组比较,三拗汤可以降低外周血、BALF中EOS的水平(P<0.05,P<0.01)及气道阻力(RI)(P<0.05,P<0.01),改善小鼠肺组织损伤,下调小鼠肺组织中TRPV2的mRNA和蛋白表达,降低BALF中IL-4,IL-10,NGF,PGD2水平(P<0.05,P<0.01)。上述三拗汤干预哮喘模型的研究表明,该方能够降低哮喘小鼠的炎症水平,改善肺功能,减轻肺损伤,其机制可能与调节肺组织中TRPV2表达、降低相关Th2细胞因子及神经递质水平有关,为其治疗哮喘提供了科学依据。

To observe the efficacy of San′ao Decoction(SAD)in diffusing the lung and relieving asthma,and its intervention effect on the expression of transient receptor potential V2(TRPV2)during alleviating asthma,this study replicated an ovalbumin(OVA)-induced asthmatic mice model,and investigated the intervention effect of SAD on the airway inflammation and airway hyperresponsiveness.The regulatory mechanisms of SAD on the mRNA and protein expressions of TRPV2 in lung tissues and the levels of interleukin-4(IL-4),-10(IL-10),nerve growth factor(NGF),prostaglandin D2(PGD2)in bronchoalveolar lavage fluid(BALF)were discussed.Compared with the control group,the model group showed typical asthmatic phenotype,the level of eosinophils(EOS)in peripheral blood and BALF as well as the airway hyperresponsiveness were increased(P<0.01),and pathological damage in lung tissue was serious.The mRNA and protein expressions of TRPV2 in lung tissue were increased significantly,while the levels of IL-4,IL-10,NGF and PGD2 in BALF were elevated(P<0.05,P<0.01).SAD could relieve bronchial asthma manifested as repaired lung patholo-gical changes(P<0.05),reduce the level of EOS in blood and BALF(P<0.05,P<0.01),and improve pulmonary resistance and lung compliance(P<0.05,P<0.01).SAD could also regulate the inflammatory cytokine levels of IL-4,IL-10,NGF,PGD2 in BALF,and reduce the gene and protein expression of TRPV2 in the lung tissue(P<0.05,P<0.01).It is verified that SAD could reduce the lung inflammation,and improve lung function in asthmatic mice.The regulatory mechanism of SAD on asthma induced by OVA might be related to the regulation of TRPV2 expression and the induced decrease of Th2-related cytokines and neuropeptides,which provides the evidences for the treatment of asthma with SAD.