黄芪注射液对哮喘大鼠p38蛋白激酶和白细胞介素-5表达的影响

Protective effects and mechanism of astragalus injection on asthmatic rats

目的:探讨黄芪注射液对哮喘大鼠p38蛋白激酶(p38 MAPK)和白细胞介素-5(IL-5)表达的影响。方法:应用鸡卵清蛋白(OVA)腹腔注射致敏和反复超声雾化吸入复制大鼠哮喘模型。40只大鼠随机分成5组:正常对照组,哮喘模型组和黄芪注射液低、中、高剂量组(2.5、5.0、10.0mL/kg)。分别采用酶联免疫吸附法(ELISA)、原位分子杂交方法和蛋白质印迹检测支气管肺泡灌洗液(BALF)IL-5含量、肺组织IL-5 mRNA和磷酸化p38 MAPK表达的变化,并观察BALF中炎症细胞计数、分类以及肺组织病理学变化。结果:哮喘模型组大鼠BALF中炎症细胞计数、IL-5含量和肺组织中IL-5 mRNA及磷酸化p38 MAPK表达均较正常对照组显著增加(P<0.01);黄芪干预组的上述改变较哮喘模型组显著降低(P<0.01),肺组织病理学损伤程度明显减轻,黄芪注射液低、中、高剂量组之间差异无统计学意义。肺组织磷酸化p38 MAPK表达水平与BALF中嗜酸性粒细胞(EOS)计数和IL-5、IL-5 mRNA含量之间分别呈显著正相关(r=0.62、0.69、0.74,P<0.01)。结论:p38 MAPK可能参与了支气管哮喘的发病过程。黄芪对哮喘的治疗作用可能部分与抑制p38 MAPK的磷酸化活化、降低炎症介质释放、减轻炎症细胞浸润有关。

AIM： To explore the protective effects and mechanism of astragalus injection on asthmatic rats. METHODS： OVA was injected intraperitoneally and inhaled to produce the asthmatic rat models. Forty vats were randomly divided into five groups： control group, asthma group and astvagalus groups of high, medium and low dose. The concentration of IL-5 in BALF and the expression of IL-5 mRNA, phospho-p38 MAPK in lung tissue were respectively measured by ELISA, in situ hybridization staining and Western blot. The number of inflammatory cell in BALF was calculated and histopathology changes were observed. RESULTS： The number of inflammatory cell and the concentration of IL-5 in BALF and the expression of IL- 5 mRNA, phospho-p38 MAPK in lung tissue were higher in asthmatic rat group than those in normal con- trol（ P 〈 0.01） ; and those in astragalus rat group were lower than in asthmatic rat group（ P 〈 0.01）. The histopathology damage was alleviated in astragalus rat group. The effieacies in the astragalus groups of high, medium and low dose were similar, showing no insignificant difference among them. The expression of phospho-p38 MAPK has positive correlation with the number of eosinophil and the concentration of IL-5, the expression of IL-5 mRNA （ r = 0.62,0.69,0.74, P 〈 0.01）. CONCLUSION： p38 MAPK may play a role in pathological process of asthma. Astragalus could effectively treat asthma by inhibiting the expression of phospho-p38 MAPK and IL-5, and decreasing the number of inflammatory cells.