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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(P<0.01)和嗜酸性粒细胞数(eosinophils number,EOS)(P<0.05);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(P<0.01或P<0.05)。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(P<0.01或P<0.05),小鼠BALF中IL-4和IL-5水平显著减弱(P<0.01);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。
The efficacy of statins on airway inflammation in asthmatic mice is not clear at present, and its mechanism of anti-inflammatory activity is different from the cholesterol-lowering effect of this class of drugs. Oral administration of high dose simvastatin (simvastatin, Sim) shows toxic side effects, if designed into a spray inhalation, the toxicity was significantly reduced. This study was divided into: NS-vehicle, model group [ovalbumim (OVA) -vehicle], Sim treatment group and dexamethasone (DXM) positive control group. It is hypothesized that Sim has inhaled biologically significant anti-inflammatory activity. BALB / c female mice were sensitized with ovalbumim (OVA) and challenged with asthma model. The mice were injected intraperitoneally with Sim-inhalation (5 mg · m L -1, ih, 15 min) mg · kg -1, ip) and intragastric administration (40 mg · kg -1, ig). The results showed that Sim could significantly reduce the total number of leukocytes (P <0.01) and eosinophils number (EOS) in alveolar lavage fluid (BALF) of mice with asthma Simultaneously, pretreatment with different dosages of Simvastatin (1, 5 and 20 mg · mL -1, ih) could reduce the total number of BALF leukocytes and the number of EOS (P <0.01 or P <0.05), respectively. The effect intensities of Sim (5 and 20 mg · mL -1, h) were similar to those of DXM with the increase of dose and inhibition of inflammatory cells. Simultaneous treatment with Sim (5 and 20 mg · mL -1), ih ) Pretreatment could decrease the mRNA expression of interleukin-4 (IL-4) and interleukin-5 (IL-5) in lung tissue of mice (P <0.01 or P < The levels of IL-4 and IL-5 in BALF were significantly decreased in mice (P <0.01). The levels of IL-4 in BALF in mice pretreated with Sim (1 mg · mL -1) The decrease of IL-5 level was lower than Sim (5 and 20 mg · m L -1) group. The above results show that inhalation of different doses of Sim can inhibit airway inflammatory response for the statins in inflammatory diseases such as asthma provide an experimental basis.