雾化吸入不同剂量辛伐他汀对哮喘模型小鼠气道炎症的影响

发布时间：2018-03-15 03:23

  本文选题：气道炎症　切入点：辛伐他汀　出处：《药学学报》2017年08期 　论文类型：期刊论文

【摘要】：他汀类药物对哮喘模型小鼠气道炎症的多效性目前尚不明确,其抗炎活性机制与本类药物降低胆固醇作用不同。口服高剂量辛伐他汀(simvastatin,Sim)可见毒副反应,若设计成雾化吸入剂,其毒性反应则明显减轻。本研究分为:空白对照组(NS-vehicle)、模型组[ovalbumim(OVA)-vehicle]、Sim治疗组和地塞米松(dexamethasone,DXM)阳性对照组。假设Sim经雾化吸入给予具有生物学意义的抗炎活性。BALB/c雌性小鼠以卵白蛋白(ovalbumim,OVA)致敏、攻击制作哮喘模型,分别运用Sim雾化吸入(5 mg·m L~(-1),ih,15 min)、腹腔注射(40 mg·kg~(-1),ip)和灌胃(40 mg·kg~(-1),ig)等途径干预。结果表明,不同途径给予Sim均可显著降低哮喘模型小鼠肺泡灌洗液(alveolar lavage fluid,BALF)中白细胞总数(P0.01)和嗜酸性粒细胞数(eosinophils number,EOS)(P0.05);Sim不同剂量(1、5和20 mg·mL~(-1),ih)预处理均可不同程度减少BALF白细胞总数、EOS数(P0.01或P0.05)。随着剂量增加,抑制炎症细胞作用增强,Sim(5和20 mg·mL~(-1),h)作用强度与DXM相近;不同剂量Sim(5和20 mg·mL~(-1),ih)预处理可降低小鼠肺组织白细胞介素-4(interleukin-4,IL-4)和白细胞介素-5(interleukin-5,IL-5)mRNA表达(P0.01或P0.05),小鼠BALF中IL-4和IL-5水平显著减弱(P0.01);Sim(1 mg·mL~(-1))预处理组小鼠BALF的IL-4水平略有下降但差异无显著性,IL-5水平下降幅度低于Sim(5和20 mg·m L~(-1))组。上述结果表明雾化吸入不同剂量Sim均可抑制气道炎症反应,为他汀类药物在哮喘等炎症性疾病中的应用提供实验依据。
[Abstract]:The pleiotropic effects of statins on airway inflammation in mice models of asthma is unclear, its anti-inflammatory activity and the mechanism of different drugs to reduce cholesterol. High dose oral simvastatin (simvastatin, Sim) visible side effects, if designed atomized inhalation toxicity, is significantly reduced. This research is divided into: blank control group (NS-vehicle), [ovalbumim model group (OVA -vehicle]), Sim treatment group and dexamethasone (dexamethasone, DXM) positive control group. If Sim by atomization inhalation given anti-inflammatory activity of.BALB/c female mice with biological significance by ovalbumin (ovalbumim, OVA) sensitization, making attack asthma model, respectively using Sim inhalation (5 mg m L~ (-1), Ih, 15 min), intraperitoneal injection (40 mg - kg~ (-1), and IP) by gavage (40 mg kg~ (-1), Ig) and other interventions. The results show that the different ways for Sim could reduce the asthma model 榧犺偤娉＄亴娲楁恫(alveolar lavage fluid,BALF)涓�鐧界粏鑳炴�绘暟(P0.01)鍜屽棞閰告，

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