目的 制备槲皮素脂质体以提高水溶性，研究槲皮素脂质体对脂多糖（LPS）诱导的小鼠炎症性肺损伤的作用。方法 采用薄膜分散法将槲皮素包裹于脂质体中，使用粒度分析仪测定其粒径和电位，使用透射电镜观察脂质体形貌特征。将20只C57BL/6小鼠随机分为5组：对照组、模型组、空白脂质体组、槲皮素（20mg·kg^-1）组和槲皮素脂质体（以槲皮素计20mg·kg^-1）组，每组4只。对照组不做处理，其余各组ip 3mg·kg^-1LPS，2h后ip相应药物，24h后取出肺组织进行苏木素-伊红染色观察肺组织病理变化；Westernblotting法检测白细胞介素（IL）-1β蛋白表达；实时荧光定量PCR（qRTPCR）法检测IL-1β、IL-6、肿瘤坏死因子-α（TNF-α）的mRNA表达。结果 槲皮素脂质体呈圆球状，粒径135nm，多分散系数0.260，电位（-4.28±0.66）mV。与模型组比较，槲皮素脂质体20mg·kg^-1能显著改善炎症引发的肺部结构变化，减轻免疫细胞浸润肺组织导致的肺泡壁增厚和肺泡结构紊乱，而槲皮素20mg·kg^-1没有表现出治疗效果；与模型组比较，槲皮素脂质体20mg·kg^-1可显著抑制肺组织成熟IL-1β蛋白表达（P＜0.01），显著下调IL-1β、IL-6、TNF-α的mRNA表达（P＜0.01），而槲皮素20mg·kg^-1不具有抑制作用。结论 脂质体制剂增强了槲皮素对小鼠肺部炎症的抑制作用，减轻了LPS引起的肺组织损伤。

Objective To improve the water solubility of free quercetin via liposomal encapsulation and investigate the effects of quercetin-loaded liposomes on inflammatory lung injury in mice. Methods The quercetin-loaded liposome was prepared via the thinfilm dispersion method. The particle size and potential of liposomes were measured by particle size analyzer, and the morphology of liposomes was observed by transmission electron microscopy. Twenty wildtype mice were randomly allocated into five groups: control group, model group, blank liposome group, quercetin (20 mg· kg^-1) group, and quercetin-loaded liposome (20 mg· kg^-1) group, with four mice for each group. The mice, except control group, were ip administered with 3 mg· kg^-1 of LPS followed by the drug treatment 2h later, and the lung tissues were collected 24h after the LPS challenge. The pathological changes in lung tissues were determined by hematoxylin-eosin staining. The expression of interleukin (IL)-1β was detected by Western blotting. Real-time fluorescence quantitative PCR (qRT-PCR) was used to detect the mRNA expression of IL-1β, IL-6 and tumor necrosis factor-α (TNF-α). Results Compared with model group, quercetin-loaded liposome 20 mg·kg^-1 could significantly improve the pulmonary structural changes induced by inflammation, and alleviate the alveolar wall thickening and alveolar structure disorder caused by the infiltration of immune cells into the lung tissue, while quercetin 20 mg·kg^-1 showed no therapeutic effect. Compared with model group, quercetin-loaded liposome 20 mg·kg^-1 could significantly inhibit the expression of IL-1β protein in mature lung tissue (P<0.01), and significantly down-regulate the mRNA expressions of IL-1β, IL-6 and TNF-α (P<0.01), but quercetin 20 mg·kg^-1 had no inhibitory effect. Conclusions Liposome enhanced the inhibitory effect of quercetin on lung inflammation and reduced lung tissue injury induced by LPS.

R283.6;R285.5

国家自然科学基金资助项目（81300059）