本文選題：氣道炎癥　切入點(diǎn)：辛伐他汀　出處：《藥學(xué)學(xué)報(bào)》2017年08期 　論文類型：期刊論文

【摘要】：他汀類藥物對(duì)哮喘模型小鼠氣道炎癥的多效性目前尚不明確,其抗炎活性機(jī)制與本類藥物降低膽固醇作用不同。口服高劑量辛伐他汀(simvastatin,Sim)可見(jiàn)毒副反應(yīng),若設(shè)計(jì)成霧化吸入劑,其毒性反應(yīng)則明顯減輕。本研究分為:空白對(duì)照組(NS-vehicle)、模型組[ovalbumim(OVA)-vehicle]、Sim治療組和地塞米松(dexamethasone,DXM)陽(yáng)性對(duì)照組。假設(shè)Sim經(jīng)霧化吸入給予具有生物學(xué)意義的抗炎活性。BALB/c雌性小鼠以卵白蛋白(ovalbumim,OVA)致敏、攻擊制作哮喘模型,分別運(yùn)用Sim霧化吸入(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)等途徑干預(yù)。結(jié)果表明,不同途徑給予Sim均可顯著降低哮喘模型小鼠肺泡灌洗液(alveolar lavage fluid,BALF)中白細(xì)胞總數(shù)(P0.01)和嗜酸性粒細(xì)胞數(shù)(eosinophils number,EOS)(P0.05);Sim不同劑量(1、5和20 mg·mL~(-1),ih)預(yù)處理均可不同程度減少BALF白細(xì)胞總數(shù)、EOS數(shù)(P0.01或P0.05)。隨著劑量增加,抑制炎癥細(xì)胞作用增強(qiáng),Sim(5和20 mg·mL~(-1),h)作用強(qiáng)度與DXM相近;不同劑量Sim(5和20 mg·mL~(-1),ih)預(yù)處理可降低小鼠肺組織白細(xì)胞介素-4(interleukin-4,IL-4)和白細(xì)胞介素-5(interleukin-5,IL-5)mRNA表達(dá)(P0.01或P0.05),小鼠BALF中IL-4和IL-5水平顯著減弱(P0.01);Sim(1 mg·mL~(-1))預(yù)處理組小鼠BALF的IL-4水平略有下降但差異無(wú)顯著性,IL-5水平下降幅度低于Sim(5和20 mg·m L~(-1))組。上述結(jié)果表明霧化吸入不同劑量Sim均可抑制氣道炎癥反應(yīng),為他汀類藥物在哮喘等炎癥性疾病中的應(yīng)用提供實(shí)驗(yàn)依據(jù)。
[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＄亴媧楁恫(alveolar lavage fluid,BALF)涓櫧緇嗚優(yōu)鎬繪暟(P0.01)鍜屽棞閰告，

本文編號(hào)：1614221