预先给予盐酸氨溴索对吸烟所致支气管炎大鼠气道炎症的影响

The Effects of Pretreatment with Ambroxol on Airway Inflammation in Rats with Chronic Bronchitis Induced by Smoking

目的探讨细胞间黏附分子-1(ICAM-1)在吸烟诱导的慢性支气管炎模型大鼠气道炎症中的作用,以及盐酸氨溴索预先给药对慢性支气管炎模型大鼠气道炎症的影响及其机制。方法将雄性Wistar大鼠30只随机分为正常对照组、吸烟模型组和氨溴索干预组各10只。采用单纯吸烟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每天预先腹腔内注射氨溴索,35mg·kg-1,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,免疫组化方法检测ICAM-1在各组支气管肺组织中的表达。结果模型组病理形态学改变符合人类慢性支气管炎特点,支气管上皮细胞、肺泡上皮细胞及肺毛细血管内皮细胞ICAM-1表达强度与BALF中白细胞总数、中性粒细胞数成显著正相关(均P<0.01);与正常对照组比较,模型组支气管上皮细胞、肺泡上皮细胞及肺毛细血管内皮细胞ICAM-1表达强度明显增强(均P<0.01);与模型组比较,氨溴索干预组支气管上皮细胞、肺泡上皮细胞及肺毛细血管内皮细胞ICAM-1表达强度明显减弱(均P<0.01)。结论吸烟诱导的慢性支气管炎模型大鼠气道炎症与ICAM-1表达上调有关。氨溴索可能通过下调ICAM-1表达,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。

Objective To explore the role of intercelluar adhesion molecule-1 （ ICAM-1 ） on airway inflammation in rats with chronic bronchitis induced by smoking and study the effect of pretreatment with ambroxol and possible mechanism. Methods Male Wistar rats were randomly divided into three groups： the control group, smoking group, ambroxol intervention group. The rat model of chronic bronchitis was established by smoking only. For ambroxol intervention group, rats were pretreated with ambroxol through peritoneal injection at 35 mg · kg^-1·d^-1 for 75 days, six days each week. The histopathologic changes in hemotoxylin and eosin （ HE ） stained bronchopuhnonary tissues were observed under optical microscope; total cell counts and differential analysis were performed in bronchoalveolar lavage fluid （BALF） ; the expression of ICAM-1 was detected by imnmnohistochemistry. Results The pathological change of model group was in consistent with that of human chronic bronchitis. The expression of ICAM-1 on bronchi and alveolar epithelial and bronchopulmonary capillary endothelial cells were positively correlated with the leukocyte numbers and neutrophil in BALF in the model group （P 〈 0.01 ）. The expression of ICAM-1 in the model group significantly increased as compared with the control group（ P 〈 0.01 ） ; which significantly decreased in atnbroxol intervention group compared with the model group （ P 〈 0.01 ）. Conclusion ICAM-1 may be involved in the process of airway inflammation in rats with chronic bronchitis induced by smoking; ambroxol might have some effects on ameliorating airway inflammation by down-regulating the expression of ICAM-1 and inhibiting the aggregation of neutrophil.