川芎嗪对致敏大鼠气道炎症气道重塑的影响和作用机制

Effect of Ligustrazine on airway inflammation and airway remodeling in asthmatic rats

目的探讨川芎嗪通过调节GATA-3和白细胞介素(IL)-5,抑制致敏大鼠气道炎症和气道重塑的分子机制。方法32只Wistar大鼠随机分成健康组、哮喘组、川芎嗪组和地塞米松(DXM)组,每组8只。苏木素-伊红(HE)染色行肺组织病理学检查、嗜酸性粒细胞计数及气道平滑肌(ASM)厚度测定;免疫组织化学两步法测定肺组织GATA-3和IL-5的表达;行肺组织GATA-3、IL-5表达与气道炎症反应间的相关性分析。结果川芎嗪和地塞米松可有效减少哮喘肺组织嗜酸性粒细胞数量和减轻平滑肌厚度,与哮喘组比较,差异有统计学意义(P<0.05);两个干预组肺组织中GATA-3和IL-5的表达较哮喘组明显减少,差异有统计学意义(P<0.05);肺组织GATA-3和IL-5表达与肺组织中嗜酸性粒细胞计数及平滑肌厚度呈正相关。结论川芎嗪可降低哮喘大鼠肺组织GATA-3和IL-5的表达,有效抑制哮喘的气道炎症,改善气道壁重塑。

Objective To investigate the molecular mechanism underlying inhibitory effect of Ligustrazine on allergic airway inflammation and airway remodeling in asthmatic rats through modulation of GATA-3 and interleukin-5 （IL-5）. Methods Thirty-two healthy Wister rats were randomly divided into 4 groups： the normal group （n=8）, the asthma model group（n=8）, the Ligustrazine group（n=8）, and the dexamethasone （DXM）group（n=8）. By HE stain, pathologic changes of lung tissue were observed. The counts of eosinophil（Eos） and the thickness of airway smooth muscle in lung tissue were measured. The expressions of GATA-3 and IL-5 in lung tissue were measured by two-step immunohistochemistry assay and the correlation between GATA-3, IL-5 and airway inflammation was analyzed. Results Compared with the asthma model group, Eos count and the thickness of airway smooth muscle of the lung tissue in the groups treated with Ligustrazine and dexamethasone were significantly decreased （P〈0.05）. The two treated groups showed significantly lowered expression of GATA-3 and IL-5 than did the asthma group （P〈0.05）. Additionally, the expression of GATA-3 and IL-5 were positively correlated with airway inflammatory response. Conclusion Ligustrazine could inhibit airway inflammation and improve airway remodeling in asthma by down-regulating the expression of GATA-3 and IL-5.