金振口服液对咳嗽高敏感性豚鼠气道神经性炎症的作用及机制研究

Effects and Mechanism of Jinzhen Oral Liquid on Airway Neurogenic Inflammation in Cough Hypersensitivity Guinea Pigs

目的研究金振口服液(Jinzhen oral liquid,JZOL)对咳嗽高敏感性模型豚鼠气道神经性炎症和咳嗽的影响及其作用机制。方法将48只豚鼠按随机数字表法分为模型组、空白对照组、JZOL高剂量组、JZOL中剂量组、JZOL低剂量组和阿莫西林组6组,每组各8只。制备咳嗽高敏感性模型,给药后观察各组咳嗽敏感性;酶联免疫吸附测定法(Enzyme-linked immunosorbent assay,ELISA)检测血清免疫球蛋白E(Immunoglobulin E,IgE)、白细胞介素-5(Interleukin-5,IL-5)含量;实时荧光定量PCR(Quantitative real-time PCR,qPCR)技术测定气管组织瞬时受体电位锚蛋白1(Transient receptor potential ankyrin 1,TRPA1)、P物质(Substance P,SP)、神经激肽A(Neurokinin A,NKA)和嗜酸性粒细胞趋化蛋白(Eotaxin,EOT)mRNA水平;苏木精-伊红(Hematoxylin-eosin,HE)染色法观察肺组织病理变化。结果与模型组比较,JZOL可以降低咳嗽敏感性;血清IgE和IL-5含量虽未见显著差异,但JZOL具有明显下调趋势,作用强度较阿莫西林明显;JZOL可抑制气管组织中EOT、SP、NKA和TRPA1 mRNA表达;JZOL对肺组织病理变化有改善作用,病变程度由高至低依次为JZOL中剂量组、阿莫西林组、JZOL低剂量组和JZOL高剂量组。结论JZOL可能通过TRPA1通道,下调SP、NKA和EOT基因表达,降低血清炎症因子和免疫球蛋白水平,改善气道神经性炎症。

Objective To explore the effects and mechanism of Jinzhen Oral Liquid(JZOL)on airway neurogenic inflammation and cough in a guinea pig model with cough hypersensitivity.Methods Forty-eight guinea pigs were randomly divided into six groups(n=8 per group):the model group,blank control group,high-dose JZOL group,medium-dose JZOL group,low-dose JZOL group,and amoxicillin group.After establishing the cough hypersensitivity model,cough sensitivity was observed post-administration in each group.Serum levels of immunoglobulin E(IgE)and interleukin-5(IL-5)were measured using enzyme-linked immunosorbent assay(ELISA).Quantitative real-time PCR(qPCR)was used to assess the mRNA expression levels of transient receptor potential ankyrin 1(TRPA1),substance P(SP),neurokinin A(NKA),and eotaxin(EOT)in tracheal tissues.Hematoxylin-eosin(HE)staining was conducted to observe the pathological changes in lung tissues.Results Compared with the model group,JZOL significantly reduced cough sensitivity.Although there were no statistically significant differences in serum IgE and IL-5 levels,JZOL exhibited a notable downward trend in these markers,with stronger efficacy than amoxicillin.JZOL inhibited the expression of EOT,SP,NKA,and TRPA1 mRNA in tracheal tissue.Additionally,JZOL improved lung tissue pathology,with the severity of lesions decreasing in the following order:medium-dose JZOL group,amoxicillin group,low-dose JZOL group,and high-dose JZOL group.Conclusion JZOL may alleviate airway neurogenic inflammation by downregulating the expression of SP,NKA,and EOT through the TRPA1 pathway,reducing serum inflammatory factors and immunoglobulin levels.