麻杏石甘汤对哮喘模型大鼠肺组织STAT4及其mRNA表达的影响

摘要

目的 研究麻杏石甘汤对哮喘模型大鼠肺组织STAT4及其mRNA表达的影响,探讨其在哮喘治疗中的作用及可能机制.方法 将55只SPF级SD大鼠随机分为5组,对照组(A组)、哮喘组(B组)、高、中、低剂量麻杏石甘汤+哮喘组(C组、D组、E组),每组1 1只.采用卵蛋白(OVA)腹腔注射致敏与雾化吸入激发法制作哮喘模型.留取肺泡灌洗液(BALF)测定IL-12及IL-13水平;并取肺组织标本HE染色后观察气道炎症,免疫组化法及原位杂交法分别检测STAT4及其mRNA表达.结果 (1)哮喘组大鼠BALF中IL-13水平升高,IL-12水平下降,肺组织炎症细胞浸润明显.(2)STAT4及STAT4 mRNA在各组大鼠气道平滑肌及血管肌层中均有表达,正常对照组呈阳性表达,哮喘组阳性表达最弱.(3)麻杏石甘汤干预后哮喘大鼠IL-13水平下降,IL-12水平上升,炎症反应减轻;STAT4表达上调,其中高剂量组与哮喘组比较差异有统计学意义(P＜0.05);高剂量、中剂量麻杏石甘汤组STAT4 mRNA表达与哮喘组比较差异均有统计学意义(均P＜0.05).结论 卵蛋白致敏大鼠气道及血管肌层STAT4表达受抑制,麻杏石甘汤可能通过上调STAT4及其mRNA的表达,减轻哮喘大鼠气道炎症反应.%Objective To investigate the expression of STAT4 in asthma rats treated with Chinese medicine Maxingshigan Decoction.Methods Fifty five SPF SD rats were randomly divided into 5 groups:control group (group A),asthma group(group B),high-dose,medium-dose and low-dose Maxingshigan Decoction treatment groups (group C,group D,group E).The rat model of asthma was established by ovalbumin (OVA) challenge methods.The bronchoalveolar lavage fluid (BALF) and lung tissues were obtained.The concentrations of IL-12 and IL-13 in BALF were measured by ELISA,the inflammation of airways was observed by HE staining;the expressions of STAT4 protein and mRNA were detected by immunohistochemistry and in situ hybridization,respectively.Results Compared with the control group,the concentration of IL-13 in BALF of asthma group was higher,while it was decreased in Maxingshigan Decoction treatment groups of asthma rats.On the contrary,the concentration of IL-12 in BALF was lower in asthma group than that in control group.The IL-12 levels in BALF were increased in Maxingshigan Decoction groups,and compared with asthma rats,the levels in groups C and D were significantly elevated(P＜0.05).HE staining showed airway smooth muscle and vascular muscle hyperplasia and peripheral inflammatory cells infiltration in asthma rats.Maxingshigan Decoction dose-dependently alleviated the pathological changes in asthma rats.STAT4 and its mRNA were expressed in airway smooth muscles and vascular muscle layers in all groups.The expression of STAT4 in Maxingshigan Decoction groups was higher than that in control group,and the expression of STAT4 protein in group C was significantly higher than that in asthma group (P＜0.05).The expression of STAT4 mRNA in groups C and D were significantly up-regulated compared with the asthma group (P＜0.05).Conclusion Chinese medicine Maxingshigan Decoction can reduce airway inflammation in asthma rats through up-regulation of STAT4 expression.