木犀草素抑制哮喘大鼠气道炎症的机制研究

目的探讨木犀草素抑制哮喘大鼠气道炎症的可能机制.方法取健康清洁级Wistar大鼠60只,随机分为木犀草素组、哮喘组、对照组,每组各20只.木犀草素组、哮喘组建立大鼠哮喘模型,建模过程中每次激发后1h给予哮喘组和对照组腹腔注射生理盐水,木犀草素组腹腔注射1 mg/kg的木犀草素.光镜下观察大鼠肺组织病理变化,测定支气管肺泡灌洗液中的细胞数及IL-4水平;免疫组化法检测p38MAPK,PPARγ蛋白表达情况;RTPCR检测p38MAPK,PPARγ的相对表达量.结果 3组大鼠支气管基底膜周径之间差异无统计学意义(P0.05);哮喘组大鼠平滑肌厚度、管壁厚度均明显高于对照组及木犀草素组大鼠(P0.05).哮喘组大鼠细胞总数、嗜酸粒细胞数、中性粒细胞数均明显高于木犀草素组和对照组(P0.05);木犀草素组细胞总数、嗜酸粒细胞数、中性粒细胞数均明显高于对照组(P0.05);哮喘组IL-4含量明显高于木犀草素组及对照组(P0.05);哮喘组大鼠p38MAPK蛋白表达明显高于对照组,PPARγ蛋白表达明显低于对照组(P0.05);木犀草素组大鼠p38MAPK蛋白表达明显低于哮喘组,PPARγ蛋白表达明显高于哮喘组(P0.05).哮喘组大鼠p38MAPK mRNA相对表达量明显高于对照组,木犀草素组表达量明显低于哮喘组(P0.05);哮喘组大鼠PPARγmRNA相对表达量明显低于对照组,木犀草素组表达量明显高于哮喘组(P0.05).结论木犀草素可能通过影响PPARγ表达和p38MAPK信号通路而发挥抑制哮喘大鼠气道炎症的作用.

On Inhibition Mechanism of Luteolin on Airway Inflammation in Asthmatic Rats

Objective To explore the possible inhibition mechanism of luteolin on airway inflammation in asthmatic rats. Method Sixty healthy Wistar rats were randomly divided into 3 groups, luteolin group, asthma group and control group, with 20 rats in each group. At the 1st hour after each excitation in the process of modeling,the asthma group and control group accepted intraperitoneal injection of saline,and the luteolin group was administrated with 1 mg/kg of luteolin. The pathological changes of lung tissue were observed under light microscope,and the cell number and IL-4 level in bronchoalveolar lavage fluid were measured. The expressions of PPARγ and p38MAPK were detected by immunohistochemistry,and the relative expressions of p38MAPK and PPARγ were detected by RT-PCR. Results The bronchial basement membrane perimeter of the rats in three groups showed no significant difference ( P>0 . 05 );but the thicknesses of smooth muscle and tube wall of the asthmatic rats were significantly higher than those in the control group and luteolin treated rats ( P<0 . 05 ) . The number of total cells,eosinophil cell and neutral granular cell of the rats in asthma group were significantly higher than those of the luteolin group and the control group ( P<0 . 05 ) , the cells number of luteolin group was significantly higher than those of the control group (P <0. 05),and the content of IL-4 in asthma group was significantly higher than that of luteolin group and control group (P<0. 05). Compared with the control group,the expressions of p38MAPK and PPARγ in asthma rats were significantly higher(P <0. 05). The expression of p38MAPK in luteolin group was much lower than the asthma group,and the expression of PPARγ is higher (P<0. 05). The relative expression of p38MAPK mRNA in asthmatic group was significantly higher than that of the control group,and the expression in luteolin group was significantly lower than that in the asthma group (P<0. 05). The relative expression of PPAR mRNA in asthma group was significantly lower than that of the control group, and the expression in luteolin group was significantly higher than that in the asthma group (P<0. 05). Conclusion Luteolin may inhibit the airway inflammation in asthmatic rats by influencing the expression of PPARγ and the signal pathway of p38MAPK.