盐酸氨溴索对吸烟诱导的支气管炎大鼠MIP-2的影响

Effect of pretreatment with Ambroxol on MIP-2 of rats with chronic bronchitis induced by smoking

目的探讨巨噬细胞炎性蛋白-2(MIP-2)在吸烟诱导的慢性支气管炎大鼠模型气道炎症中的作用,以及盐酸氨溴索预先给药对慢性支气管炎大鼠模型气道炎症的影响及其机制。方法雄性Wistar大鼠随机分为3组:正常对照组、吸烟模型组和氨溴索干预组。采用单纯吸烟的方法建立慢性支气管炎大鼠模型。氨溴索干预组自模型建立开始时每天预先腹腔内注射氨溴索[35mg/(kg·d)]1次,每周6d,连续75d后处死大鼠。光镜下观察支气管肺组织病理形态学改变。分析支气管肺泡灌洗液(BALF)细胞计数和分类;用ELISA法测定肺组织匀浆MIP-2的含量。结果模型组病理形态学改变符合人类慢性支气管炎的特点。模型组肺组织匀浆MIP-2与BALF中白细胞总数、中性粒细胞数成显著正相关(分别为r=0.706及r=0.819;均P<0.01)。与正常组比较,模型组肺组织匀浆MIP-2含量明显升高(P<0.01)。与模型组比较,氨溴索干预组肺组织匀浆MIP-2含量明显降低(P<0.01)。结论吸烟诱导的慢性支气管炎大鼠模型气道炎症与MIP-2的特异性趋化作用有关;氨溴索可能通过减少MIP-2的合成,抑制中性粒细胞在气道中的聚集、活化而减轻气道炎症反应。

[Objectives] To discuss the role of Macrophage inflammatory protein-2 （MIP-2） in airway inflammation in rats with chronic bronchitis induced by smoking and to study the effect of pretreatment with Ambroxol on rats with chronic bronchitis and asses the possible mechanism. [ Methods ] Male Wistar rats were randomly divided into three experiment groups： the control group, smoking model group, Ambroxol intervention group. The rats model of chronic bronchitis were established by smoking purely. For Ambroxol intervention group, pretreatment with Ambroxol through peritoneal injection was given 35 mg/kg·d for 75 days before the rats were put to death, six days every week. The histopathologic changes stained with hemotoxylin and eosin （HE） of bronchopulmonary tissues were observed under optical microscope; total cell counts and differential analysis were performed in BALF; the concentration of MIP-2 in homogenate of pulmonary tissues were also measured with ELISA. [Results] Pathological changes of smoking model group consistents with that of chronic bronchitis. The concentration of MIP-2 in homogenate of pulmonary tissues were postively correlated with the leukocyte numbers and neutrophil in BALF in the model group, （r =0.706 and r =0.819 respectively; both P 〈0.01）. The concentration of MIP-2 in homogenate of pulmonary tissues in the model group significantly increased as compared with the control group （P 〈0.01）. The concentration of MIP-2 in homogenate of pulmonary tissues in Ambroxol intervention group significantly degraded as compared with the model group （P 〈0.01）. [ Conclusions ] MIP-2 may be involved in the process of airway inflammation in rats with chronic bronchitis induced by smoking; Ambroxol might have some effects on limiting airway inflammation by dimin-ishing the production of MIP-2 and inhibiting the activation of neutrophil.