长期使用β受体阻滞剂减轻小鼠哮喘模型气道炎症和粘蛋白含量
2008/06/06
β受体激动剂可致支气管扩张并抑制气道高反应性，是哮喘急性发作的缓解剂。然而长期反复使用β受体激动剂也可能增加气道高反应性（AHR）、气道炎症和死亡的风险。另一方面，有研究显示充血性心力衰竭的患者长期使用β受体阻滞剂可部分逆转心肌重构，Nguyen LP等从中得到启示，认为长期给予β受体阻滞剂有可能降低哮喘小鼠的AHR。
作者通过研究发现，给哮喘小鼠予β受体阻滞剂可降低支气管肺泡灌洗液（BALF）中总的细胞量、嗜酸性粒细胞数及IL-13, IL-10, IL-5, 及TGF-β1水平，降低上皮细胞粘蛋白含量及细胞形态变化。作者同时发现给予β受体阻滞剂7天对上述现象的抑制作用不如28天明显。该研究结果表明在慢性小鼠哮喘模型中长期给予β受体阻滞剂可降低气道炎症和上皮黏液化生，从而可能减轻气道阻塞和AHR。该研究结果提示β受体阻滞剂虽然对哮喘有即刻的不利作用，但另一方面长期应用也有可能提供有益的治疗作用。
作者通过研究发现，给哮喘小鼠予β受体阻滞剂可降低支气管肺泡灌洗液（BALF）中总的细胞量、嗜酸性粒细胞数及IL-13, IL-10, IL-5, 及TGF-β1水平，降低上皮细胞粘蛋白含量及细胞形态变化。作者同时发现给予β受体阻滞剂7天对上述现象的抑制作用不如28天明显。该研究结果表明在慢性小鼠哮喘模型中长期给予β受体阻滞剂可降低气道炎症和上皮黏液化生，从而可能减轻气道阻塞和AHR。该研究结果提示β受体阻滞剂虽然对哮喘有即刻的不利作用，但另一方面长期应用也有可能提供有益的治疗作用。
（王苹莉 浙江医科大学附属第二医院呼吸科310009 摘译）
（Am J Respir Cell Mol Biol. 2008 Mar;38(3):256-262）
Nguyen LP, Omoluabi O, Parra S, Frieske JM, Clement C, Ammar-Aouchiche Z, Ho SB, Ehre C, Kesimer M, Knoll BJ, Tuvim MJ, Dickey BF, Bond RA. Chronic exposure to beta-blockers attenuates inflammation and mucin content in a murine asthma model.
Am J Respir Cell Mol Biol. 2008 Mar;38(3):256-62
Single-dose administration of beta-adrenoceptor agonists produces bronchodilation and inhibits airway hyperresponsiveness (AHR), and is the standard treatment for the acute relief of asthma. However, chronic repetitive administration of beta-adrenoceptor agonists may increase AHR, airway inflammation, and risk of death. Based upon the paradigm shift that occurred with the use of beta-blockers in congestive heart failure, we previously determined that chronic administration of beta-blockers decreased AHR in a murine model of asthma. To elucidate the mechanisms for the beneficial effects of beta-blockers, we examined the effects of chronic administration of several beta-adrenoceptor ligands in a murine model of allergic asthma. Administration of beta-blockers resulted in a reduction in total cell counts, eosinophils, and the cytokines IL-13, IL-10, IL-5, and TGF-beta1 in bronchoalveolar lavage, and attenuated epithelial mucin content and morphologic changes. The differences in mucin content also occurred if the beta-blockers were administered only during the ovalbumin challenge phase, but administration of beta-blockers for 7 days was not as effective as administration for 28 days. These results indicate that in a murine model of asthma, chronic administration of beta-blockers reduces inflammation and mucous metaplasia, cardinal features of asthma that may contribute to airflow obstruction and AHR. Similar to heart failure, our results provide a second disease model in which beta-blockers producing an acutely detrimental effect may provide a therapeutically beneficial effect with chronic administration.
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