Turner Dawn L, Ford William R, Kidd Emma J, Broadley Kenneth J, Powell Colin
Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cathays Park, Cardiff CF10 3NB, Wales, UK.
Cardiff School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cathays Park, Cardiff CF10 3NB, Wales, UK.
Eur J Pharmacol. 2017 Apr 15;801:79-85. doi: 10.1016/j.ejphar.2017.03.004. Epub 2017 Mar 8.
Magnesium sulphate is a potential treatment for acute severe asthma. However, the mechanisms and dose-response relationships are poorly understood. The first objective of this study was to examine whether inhaled magnesium sulphate exerts bronchodilator activity measured as bronchoprotection against histamine-induced bronchoconstriction in conscious guinea-pigs alone and combined with salbutamol. Secondly, we examined whether inhaled magnesium sulphate inhibits airways inflammation and function in models of neutrophilic and eosinophilic lung inflammation induced, respectively, by inhaled lipopolysaccharide or the inhaled antigen, ovalbumin (OVA). Airway function was measured in conscious guinea-pigs as specific airway conductance (sG) by whole-body plethysmography. Anti-inflammatory activity was measured against lung inflammatory cell influx induced by OVA inhalation in OVA-sensitised animals or by lipopolysaccharide (LPS) exposure of non-sensitised animals. Airway function (sG) was measured over 24h after OVA exposure. Airway hyperresponsiveness to inhaled histamine and inflammatory cells in bronchoalveolar lavage fluid were recorded 24h after OVA or LPS challenge. Histamine-induced bronchoconstriction was inhibited by inhaled magnesium sulphate or salbutamol alone and in combination, they produced synergistic bronchoprotection. LPS-induced neutrophil influx was inhibited by 6 days pretreatment with magnesium sulphate. Early and late asthmatic responses in OVA sensitised and challenged animals were attenuated by magnesium sulphate. Lung inflammatory cells were increased by OVA, macrophages being significantly reduced by magnesium sulphate. Nebulised magnesium sulphate protects against histamine-induced bronchoconstriction in conscious guinea-pigs and exerts anti-inflammatory activity against pulmonary inflammation induced by allergen (OVA) or LPS. These properties of magnesium sulphate explain its beneficial actions in acute asthma.
硫酸镁是急性重症哮喘的一种潜在治疗方法。然而，其作用机制和剂量反应关系尚不清楚。本研究的首要目的是检验吸入硫酸镁是否具有支气管扩张活性，在清醒豚鼠中，通过测量其对组胺诱导的支气管收缩的支气管保护作用来评估，单独使用及与沙丁胺醇联合使用时的效果。其次，我们研究了吸入硫酸镁是否能抑制分别由吸入脂多糖或吸入抗原卵清蛋白（OVA）诱导的嗜中性粒细胞性和嗜酸性粒细胞性肺部炎症模型中的气道炎症和功能。通过全身体积描记法在清醒豚鼠中测量气道功能，以特定气道传导率（sG）表示。在OVA致敏动物中，通过测量吸入OVA诱导的肺部炎症细胞流入情况，或在未致敏动物中通过脂多糖（LPS）暴露，来测定抗炎活性。在OVA暴露后24小时测量气道功能（sG）。在OVA或LPS激发后24小时记录对吸入组胺的气道高反应性和支气管肺泡灌洗液中的炎症细胞。吸入硫酸镁或沙丁胺醇单独及联合使用均可抑制组胺诱导的支气管收缩，二者联合产生协同性支气管保护作用。硫酸镁预处理6天可抑制LPS诱导的中性粒细胞流入。硫酸镁可减轻OVA致敏和激发动物的早期和晚期哮喘反应。OVA可增加肺部炎症细胞，而硫酸镁可使巨噬细胞显著减少。雾化吸入硫酸镁可保护清醒豚鼠免受组胺诱导的支气管收缩，并对变应原（OVA）或LPS诱导的肺部炎症发挥抗炎活性。硫酸镁的这些特性解释了其在急性哮喘中的有益作用。
