芹菜素对哮喘小鼠转录激活蛋白3及Th<sub>2</sub>型细胞因子抑制作用的实验研究

作者	单位
庞玲玲	南京医科大学第一附属医院呼吸科
李若然	南京医科大学第一附属医院呼吸科
周林福	南京医科大学第一附属医院呼吸科
史莹	南京医科大学第一附属医院呼吸科
代文静	南京医科大学第一附属医院呼吸科
殷凯生	南京医科大学第一附属医院呼吸科

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中文摘要:

目的研究芹菜素对哮喘小鼠2型辅助性T细胞(Th2)优势应答的抑制作用及其机制。方法选择32只6周龄SPF级BALB/c小鼠,随机分为4组,每组8只:正常组(A组)、哮喘组(B组)、芹菜素高剂量治疗组〔C组,20 mg/(kg.d)〕、芹菜素低剂量治疗组〔D组,2 mg/(kg.d)〕。卵白蛋白(OVA)致敏和激发制作哮喘模型。药物治疗组以芹菜素溶于1%二甲基亚砜(DMSO)腹腔注射。小鼠末次雾化吸入24 h后,用小鼠肺功能仪检测气道对乙酰胆碱(Ach)阻力;苏木精-伊红(HE)染色观察气道炎症浸润情况;支气管肺泡灌洗液(BALF)瑞氏染色计数嗜酸性粒细胞百分比;酶联免疫吸附(ELISA)法测定血清总IgE、BALF液中Th2型细胞因子〔白细胞介素(IL)4、IL-13〕;免疫印迹(Western blot)测定肺组织中信号转导和转录激活蛋白3(GATA-3)表达水平。结果与正常组比较,哮喘组Ach气道阻力、气道炎症、BALF细胞计数和嗜酸性粒细胞分类计数、血清总IgE、BALF中IL-4、IL-13以及肺组织GATA-3蛋白表达明显增高(P<0.05)。与哮喘组比较,芹菜素治疗组各项指标均明显降低(P<0.05),而且高、低剂量组之间差异有统计学意义(P<0.05)。结论芹菜素通过降低肺组织GATA-3和Th2细胞因子的表达而降低哮喘小鼠气道炎症和气道高反应性,具有潜在的临床应用前景。

英文摘要:

Objective To investigate the inhibitory effects and mechanism of apigenin(APG) on dominant response of Th2 cells in asthma model of mice.Methods Thirty-two 6-week old healthy BALB/c mice,SPF grade,were randomly divided into four groups equally,the normal control group(A),the asthma model group(B),and the two APG groups(C and D) consisted of asthma model mice treated respectively with high-dose(20 mg/kg per day) and low-dose(2 mg/kg per day) APG given by dissolving in 1% dimethyl sulphoxide via intraperitoneal injection.The murine asthma model was established by ovalbumin(OVA) sensitization and provocation.Twenty-four hours after the last airway provocating,acetylcholine(Ach) was administered via caudalis vein for measuring airway resistance by pulmonary function detector;levels of IL-4 and IL-13 in branchoalveolar lavage fluid(BALF) and total IgE in serum were determined by enzyme-linked immunosorbent assay(ELISA);total and differential cell counts in BALF were measured by light microscopy;the airway inflammatory infiltration was detected by haematoxylin and eosin(HE) staining;and the signal transducer and activator of transcription 3(GATA-3) in the lung tissue was determined by Western blot analysis.Results As compared with Group A,the airway hyper-reactivity,airway inflammation,cell count and eosinophil percentage in BALF,levels of total serum IgE and BALF IL-4 and IL-13,and GATA-3 protein expression in the lung tissue were significantly increased in Group B(P<0.05).As compared with Group B,all the above-mentioned indices in Group C and D were lower,showing respective significant difference(P<0.05),and significant difference was also shown between the two APG treated groups(P<0.05).Conclusion APG could reduce the airway inflammation and hyper-reactivity by down-regulating the expressions of pulmonary GATA-3 and Th2 cytokines,which is a potential drug for asthma therapy.

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