柴朴汤对哮喘大鼠肺组织MAL/MAPK/ERK 通路的影响

Chaipu Decoction interferes with MAL/MAPK/ERK signal pathway in rat model of asthma

摘要:

目的 探讨柴朴汤是否通过调控T 细胞成熟相关蛋白（MAL）/ 丝裂原活化蛋白激酶（MAPK）/ 细胞外调节蛋白激酶（ERK）通路对哮喘大鼠发挥治疗作用。方法 健康SD 大鼠40 只，随机分为4 组，哮喘组、 柴朴汤组、使用柴朴汤+MAPK/ERK 通路抑制剂（PD98059）（柴抑组）、对照组，每组10 只。按照文献复制 哮喘大鼠模型，使用柴朴汤及PD98059 进行干预，采用RT-PCR 检测肺组织中MAL mRNA 的表达情况，免疫 组织化学检测肺组织中MAL、p-ERK1/2、IL-4 蛋白的表达。结果 哮喘组MAL mRNA 和蛋白表达水平最低， p-ERK1/2 及IL-4 的蛋白表达水平最高，与对照组比较，差异有统计学意义（P <0.05）。与哮喘组比较，柴朴汤 组、柴抑组MAL mRNA 和蛋白表达水平增高，p-ERK1/2 及IL-4 蛋白表达水平降低（P <0.05）。但柴朴汤组 和柴抑组MAL mRNA 和蛋白比较无差异（P >0.05），而柴抑组的p-ERK1/2 及IL-4 的蛋白表达低于柴朴汤组 （P <0.05）。结论 ① MAL/MAPK/ERK 通路参与了哮喘病理发展过程。②柴朴汤可通过上调MAL 的表达， 抑制MAPK/ERK 通路，减少炎症反应，进而延缓哮喘病变。

Abstract:

Objective To investigate the role of Chaipu Decoction in asthmatic rats and its potential mechanism on MAL/MAPK/ERK pathway. Methods Totally 40 healthy SD rats were randomly divided into asthmatic group, Chaipu Decoction group, Chaipu Decoction + MAPK/ERK pathway inhibitor (PD98059) group and control group (10 for each group). Rat models of asthma were replicated based on publications. Rats in Chaipu Decoction group and Chaipu Decoction + PD98059 group received Chaipu Decoction and PD98059, respectively. Expressions of MAL mRNA in lung tissues were detected by RT-PCR. Expressions of MAL, p-ERK1/2 and IL-4 in lung tissues were measured by immunohistochemistry. Results Expressions of MAL in asthmatic group were decreased while expression of p-ERK1/2 and IL-4 were increased significantly when compared with control group (P < 0.05). Treatment of Chaipu Decoction or PD98059 reversed decrease of MAL and increase of p-ERK1/2 and IL-4 compared with that in the asthmatic group (P < 0.05). No dramatic difference of MAL was identified between Chaipu Decoction group and Chaipu Decoction + PD98059 group (P > 0.05). Rats in Chaipu Decoction + PD98059 group experienced lower levels of p-ERK1/2 and IL-4 protein than those in Chaipu Decoction group (P < 0.05). Conclusions MAL/MAPK/ERK pathway participates in the pathogenesis of asthma. Chaipu Decoction reduces the lesion of asthma through mediating MAL/MAPK/ERK signal pathway.