Pharmaceutical Department, University of Parma, Parma, Italy.
Eur J Pharm Biopharm. 2013 Aug;84(3):566-72. doi: 10.1016/j.ejpb.2013.01.021. Epub 2013 Mar 7.
Chronic obstructive pulmonary disease (COPD) is characterised by mucus hyper-production. This pathology, together with other inflammatory contributions, leads to airway obstruction and breathing complications. Newer therapeutic approaches are of increased interest, including the use of HMG-CoA reductase inhibitors. Retrospective studies have shown that statins are effective in reducing patient mortality and blood cytokines levels. These findings suggest statins may also provide a new therapeutic approach in COPD treatment.
The aim of the present work was to study the transport of simvastatin (SV) across Calu-3 epithelial cells and to investigate its pharmacological action with respect to reduction in mucus production.
Calu-3 cells were grown under liquid covered culture (LCC) conditions for transport studies in order to demonstrate the ability of SV to transport across the monolayer. For mucus detection, cells were grown under air interface culture (AIC) conditions. Samples collected for microscope analysis were stained with alcian blue; images of the stained cell surface were acquired and the mucus was quantified as the RGBB ratio.
SV was transported through the cell monolayer and 'retained' inside the Calu-3 cells. Colour analysis of stained Calu-3 monolayers microscope-images showed that chronic administration of SV for 14 days caused a significant inhibition in mucus production.
These findings suggest that local delivery of SV directly to the lungs may provide a promising treatment and potential disease management approach of COPD, with significant effects on mucus reduction.
慢性阻塞性肺疾病（COPD）的特征是粘液过度产生。这种病理，加上其他炎症贡献，导致气道阻塞和呼吸并发症。较新的治疗方法越来越受到关注，包括使用 HMG-CoA 还原酶抑制剂。回顾性研究表明，他汀类药物可有效降低患者死亡率和血液细胞因子水平。这些发现表明他汀类药物也可能为 COPD 治疗提供新的治疗方法。
本工作的目的是研究辛伐他汀（SV）在 Calu-3 上皮细胞中的转运，并研究其在减少粘液产生方面的药理作用。
为了研究 SV 穿过单层的能力，将 Calu-3 细胞在液覆盖培养（LCC）条件下培养进行转运研究。为了检测粘液，细胞在气-液界面培养（AIC）条件下培养。用于显微镜分析的样品用阿利新蓝染色；对染色细胞表面的图像进行采集，并将粘液定量为 RGBB 比值。
SV 通过细胞单层运输，并“保留”在 Calu-3 细胞内。对染色的 Calu-3 单层显微镜图像进行颜色分析表明，辛伐他汀连续给药 14 天可显著抑制粘液产生。
这些发现表明，SV 直接向肺部局部给药可能为 COPD 提供一种有前途的治疗和潜在的疾病管理方法，对减少粘液有显著影响。
