特异性p38丝裂原活化蛋白激酶抑制剂对哮喘气道黏液高分泌的抑制作用

Inhibitory effect of specific inhibitor of p38 mitogen activated protein kinase on hyper secretion of airway mucus in asthma

目的观察p38丝裂原活化蛋白激酶(p38 MAPK)特异性抑制剂SB203580对哮喘模型小鼠气道黏液高分泌的抑制作用。方法取BABL/C小鼠40只,按随机数字表法分为哮喘组、SB203580治疗组、地塞米松治疗组和正常对照组,每组10只。高碘酸希夫(AB-PAS)特染法检测各组小鼠小支气管杯状细胞的数量,ELISA法检测支气管肺泡灌洗液中黏蛋白MUC5AC含量,RT-PCR法检测小鼠肺组织MUC5AC mRNA表达水平,并采用图像分析法进行灰度分析。结果与正常对照组相比,哮喘组的上皮杯状细胞数量、支气管肺泡灌洗液中MUC5AC含量、肺组织MUC5AC mRNA表达水平均显著增加(P<0.01)。经过SB203580和地塞米松分别干预后,上述指标均明显低于哮喘组(P<0.01),而且SB203580对杯状细胞、肺组织MUC5AC mRNA的抑制能力比地塞米松更强(P<0.01)。结论p38 MAPK特异性抑制剂SB203580在一定程度上能够抑制杯状细胞增生与MUC5AC合成,在哮喘气道黏液高分泌的防治中具有潜在的临床应用前景。

Objective To explore the inhibitory effects of SB203580, a specific inhibitor of p38 mitogen activated protein kinase （p38 MAPK） on hyper secretion of airway mucus in mice with asthma. Methods Forty BABL/C mice were randomly allocated into asthma group, SB203580 treatment group, dexamethasone treatment group and control group （sham-challenged group）. Mice in SB203580 treatment group were intraperitoneally injected with SB203580 （10mg/kg）, while those in dexamethasone treatment group were injected with dexamethasone （1mg/kg） before provocation. The number of goblet cells in small bronchi of all groups was determined after Alcian blue-periodic acid Schiff （AB-PAS） staining. The contents of MUC5AC in bronchoalveolar lavarge fluid （BALF） were evaluated with ELISA asssy. The levels of MUC5AC mRNA expression were determined with reverse transcription-polymerase chain reaction （RT-PCR） assay, and gray-scale analysis was done with image analysis method. Results Compared with the normal group, the number of airway goblet cells, the contents of MUC5AC in BALF and the level of lung MUC5AC mRNA expression in asthma group were raised significantly （P〈0.01）. The three indices in both SB203580 and dexamethasone treatment groups were lower than that in asthma group （P〈0.01）. In addition, the number of airway goblet cells and the level of lung MUC5AC mRNA expression in SB20358 treatment group declined more obviously compared with that in dexamethasone treatment group （P〈0.01）. Conclusions It can be demonstrated that SB203580, the specific inhibitor of p38 MAPK, may inhibit the proliferation of goblet cells and the synthesis of MUC5AC in mice with asthma, and the former has the strong suppressing effect on hyper secretion of airway mucus. So SB203580 may have a potential clinical perspective in the treatment of the patients with mucus hyper secretion induced by asthma.