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目的:研究氨溴索对哮喘大鼠气道炎症的影响及其可能的作用机制。方法:将30只雄性SD大鼠随机分为3组:对照组、模型组、治疗组。模型组、治疗组卵清蛋白(OVA)致敏。治疗组致敏同时给予腹腔注射氨溴索50 mg.kg-1.d-1。各组动物于最后一次雾化吸入后24 h收集支气管肺泡灌洗液(BALF)。行BALF中炎症细胞总数、PMN计数及细胞分类计数。取BALF上清液,应用酶联免疫吸附试验法测定IL-8水平。HE染色观察肺组织病理改变,免疫组织化学技术观察NF-κBp65、MMP-9、MPO在肺组织中的表达。结果:(1)模型组显示支气管、血管周围大量炎性细胞浸润,治疗组显示支气管痉挛及炎性细胞浸润明显减轻。(2)模型组BALF中炎性细胞及PMN计数、IL-8显著高于对照组(P<0.01)。治疗组BALF中炎性细胞及PMN计数、IL-8显著低于模型组(P<0.01)。(3)模型组肺组织中NF-κBp65、MMP-9、MPO的表达水平显著高于对照组(P<0.01)。治疗组大鼠肺组织中NF-κBp65、MMP-9、MPO的表达水平显著低于模型组(P<0.01)。结论:氨溴索可能是通过抑制转录因子NF-κB的活化,继而下调IL-8、MMP-9、MPO等的表达,减少PMN为主的炎症细胞在气道内的浸润,对哮喘患者发挥治疗作用。
Objective: To study the effect of ambroxol on airway inflammation in asthmatic rats and its possible mechanism. Methods: Thirty male SD rats were randomly divided into three groups: control group, model group and treatment group. Model group, treatment group ovalbumin (OVA) sensitized. The treatment group was given intraperitoneal injection of ambroxol 50 mg.kg-1.d-1 simultaneously. Bronchoalveolar lavage fluid (BALF) was collected 24 hours after the last inhalation in each group of animals. The total number of inflammatory cells in BALF, PMN count and cell count. The BALF supernatant was taken and the level of IL-8 was measured by enzyme-linked immunosorbent assay. The pathological changes of lung tissue were observed by HE staining. The expression of NF-κBp65, MMP-9 and MPO in lung tissue were observed by immunohistochemistry. Results: (1) The model group showed a large number of infiltration of inflammatory cells in the bronchi and blood vessels, the treatment group showed bronchospasm and inflammatory cell infiltration significantly reduced. (2) The number of inflammatory cells and PMN in BALF in model group was significantly higher than that in control group (P <0.01). The number of inflammatory cells and PMN in BALF in treatment group was significantly lower than that in model group (P <0.01). (3) The expression of NF-κBp65, MMP-9 and MPO in the model group was significantly higher than that in the control group (P <0.01). The expression of NF-κBp65, MMP-9 and MPO in the lung tissue of the treatment group was significantly lower than that of the model group (P <0.01). Conclusion: Ambroxol may decrease the airway infiltration of PMN-based inflammatory cells and down-regulate the expression of IL-8, MMP-9 and MPO by inhibiting the activation of transcription factor NF-κB effect.