苦参碱通过抑制Lyn/Syk信号通路治疗大鼠过敏性哮喘  

Matrine treats allergic asthma through inhibition of Lyn/Syk signaling pathway in rat’s model

作　　者：范爱欣 袁菲 唐科毅 

机构地区：[1]青岛市第五人民医院呼吸与危重症(肺病)科,266002 [2]青岛市第五人民医院变态反应科,266002 [3]青岛市第五人民医院院感科,266002

出　　处：《免疫学杂志》2023年第10期872-878,共7页Immunological Journal

基　　金：青岛市公共领域科技支撑计划(09-1-1-5-nsh)

摘　　要：目的探讨苦参碱(Mat)调节Lyn/Syk信号通路对过敏性哮喘大鼠免疫功能的影响。方法随机取12只SD大鼠作为对照组(NC组),其余大鼠参考先前文献通过卵清蛋白(OVA)造模。将造模成功的过敏性哮喘大鼠随机平分为Model组、Mat组(100 mg/kg Mat)、MLR-1023组(30 mg/kg Lyn/Syk信号通路激活剂MLR-1023)、Mat+MLR-1023组(100 mg/kg Mat+30 mg/kg MLR-1023),每组12只。NC组、Model组给予等量的生理盐水,每天1次,持续4周。收集支气管肺泡灌洗液(BALF)并进行嗜酸粒细胞计数;ELISA试剂盒检测血清和BALF液中细胞因子水平;HE染色检测肺组织病理变化;测定肺组织中组胺水平;Western blot检测Lyn/Syk通路相关蛋白水平。结果NC组大鼠肺组织染色清晰,结构正常。Model组出现大量炎性细胞浸润现象,支气管周围嗜酸粒细胞增多,上皮细胞增大、脱落。Model组较NC组血清中TNF-α、IL-4、IL-5、IL-1β和LTD-4水平,BALF中IgE、OVA sIgE、嗜酸粒细胞数量以及肺组织p-Lyn/Lyn、p-Syk/Syk、组胺水平均显著增加(P<0.05);与Model组相比,Mat组嗜酸粒细胞数量、TNF-α、IL-4、IL-5、IL-1β和LTD-4水平、IgE、OVA sIgE、组胺、p-Lyn/Lyn、p-Syk/Syk水平均显著降低(P<0.05),而MLR-1023组结果与Mat组趋势相反;MLR-1023消除了Mat对过敏性哮喘大鼠的治疗效果。结论Mat可能通过下调Lyn/Syk信号通路对过敏性哮喘大鼠免疫功能起到改善作用。To investigate the impact of matrine(Mat)on the immune function of rats with allergic asthma by regulating the Lyn/Syk signal pathway,12 SD rats were randomly selected as control group(NC group),and the other rats were modeled by ovalbumin(OVA)with reference to previous literature.The successfully modeled allergic asthma rats were randomly grouped into model group,Mat group(100 mg/kg Mat),MLR-1023 group(30 mg/kg Lyn/Syk signal pathway activator MLR-1023),and Mat+MLR-1023 group(100 mg/kg Mat+30 mg/kg MLR-1023),with 12 rats in each group.NC group and Model group were given the same amount of physiological saline once a day for 4 weeks.Bronchoalveolar lavage fluid(BALF)were collected and eosinophils were counted;the level of cytokines in serum and BALF were detected by ELISA kit;the pathological change of lung tissue was evaluated by HE staining;the histamine level in lung tissue was measured;Western blot was applied to detect the levels of Lyn/Syk pathway related proteins.Data showed that the lung tissue in NC group was stained clearly and the structure was normal.In the model group,a large number of inflammatory cells infiltrated,the eosinophils around the bronchus increased,epithelial cells enlarged and fell off.Compared with NC group,the model group demonstrated obvious increase in the number of eosinophils,the levels of TNF-α,IL-4,IL-5,IL-1βand LTD-4 in serum,the levels of IgE and OVA sIgE in BALF,and the levels of histamine,p-Lyn/Lyn and p-Syk/Syk in lung tissue(P<0.05).Matrine could reverse these pathological changes mentioned above in model rats(P<0.05),while MLR-1023 eliminated the therapeutic effect of Mat on allergic asthma rats.Taken together,Mat may improve the immune function of rats with allergic asthma by down-regulating the Lyn/Syk signal pathway.

关 键 词：苦参碱 Lyn/Syk信号通路 过敏性哮喘 免疫功能 

分 类 号：Q95-33[生物学—动物学]