噻托溴铵对慢性阻塞性肺疾病大鼠血清、肺泡灌洗液及肺组织中IL-8、TNF-α、PLA2的影响

目的研究噻托溴铵对慢性阻塞性肺疾病（简称慢阻肺）大鼠血清、肺泡灌洗液及肺组织中炎症因子水平及肺组织病理结构的影响,以证实噻托溴铵治疗慢阻肺的抗炎作用。方法采用烟熏加气管内注入内毒素法建立大鼠慢阻肺模型。将雄性SD大鼠随机分为对照组、慢阻肺组和噻托溴铵干预组,每组10只。HE染色观察大鼠肺、支气管的病理改变,测定肺平均内衬间隔（MLI）及平均肺泡数（MAN）。行支气管肺泡灌洗液（BALF）细胞计数及分类。酶联免疫吸附试验检测各组大鼠血清、BALF及肺组织中IL-8、TNF-α、磷脂酶A2（PLA2）的含量。结果慢阻肺组大鼠肺、支气管HE染色符合慢阻肺的病理改变;慢阻肺组大鼠出现明显肺气肿,噻托溴铵组也出现肺气肿,但程度较轻。慢阻肺组大鼠BALF中细胞总数、中性粒细胞及淋巴细胞比例,血清、BALF及肺组织中炎症因子水平较对照组均明显升高（P〈0.01）;噻托溴铵干预组与慢阻肺组相比,BALF中细胞总数、中性粒细胞及淋巴细胞比例,血清、BALF及肺组织中炎症因子水平均显著降低（P〈0.01）,但仍明显高于对照组（P〈0.01）。结论噻托溴铵可以通过减少炎症细胞渗出降低慢阻肺大鼠血清、BALF及肺组织中IL-8、TNF-α、PLA2水平,减轻气道及肺组织炎症,发挥抗炎作用。

Effects of Tiotropium Bromide on Inflammatory Factors in Serum,BALF and Lung Tissue of COPD Rats

Objective To investigate the changes of interleukin-8（ IL-8）,tumor necrosis factor-α（ TNF-α） and phospholipase A2（ PLA2） in serum,bronchoalveolar lavage fluid（ BALF） and lung tissue of COPD rats and the effects of tiotropium. To identify the anti-inflammatory function of tiotropium. Methods Rat COPD model was established by passive smoking as well as intratracheal instillation of lipopolysaccharide（ LPS）. Thirty male SD rats were randomly divided into a control group,a COPD group and a tiotropium bromide treatment group（ n = 10 in each group）. The pathologic changes of the lung tissue and airway were observed by HE staining. The total and differential cell counts in BALF were observed. The levels of IL-8,TNF-α,PLA2 in serum,BALF and lung tissue were measured by enzyme-linked immunosorbent assay.Results HE staining revealed that the rat COPD model was successfully established. The COPD group appeared obvious emphysema,while the treatment group appeared mild emphysema. The total inflammatory cells,the proportion of neutrophils and lymphocyte,and the levels of IL-8,TNF-α,PLA2 in serum,BALF and lung tissue in the COPD group were obviously higher than those in the control group（ P 〈 0. 01）. The total inflammatory cells,the proportion of neutrophils and lymphocyte,and the levels of IL-8,TNF-α,PLA2 in serum,BALF and lung tissue in the treatment group were significantly lower than those in the COPD group but higher than those in the control group（ P 〈 0. 01）. Conclusions Tiotropium bromide can reduce the levels of IL-8,TNF-α,PLA2 in serum,BALF and lung tissue of COPD rats by reducing the leakage of inflammatory cells,and alleviate the airway inflammation and the degree of emphysema.