目的 制備槲皮素脂質(zhì)體以提高水溶性，研究槲皮素脂質(zhì)體對(duì)脂多糖（LPS）誘導(dǎo)的小鼠炎癥性肺損傷的作用。方法 采用薄膜分散法將槲皮素包裹于脂質(zhì)體中，使用粒度分析儀測定其粒徑和電位，使用透射電鏡觀察脂質(zhì)體形貌特征。將20只C57BL/6小鼠隨機(jī)分為5組：對(duì)照組、模型組、空白脂質(zhì)體組、槲皮素（20mg·kg^-1）組和槲皮素脂質(zhì)體（以槲皮素計(jì)20mg·kg^-1）組，每組4只。對(duì)照組不做處理，其余各組ip 3mg·kg^-1LPS，2h后ip相應(yīng)藥物，24h后取出肺組織進(jìn)行蘇木素-伊紅染色觀察肺組織病理變化；Westernblotting法檢測白細(xì)胞介素（IL）-1β蛋白表達(dá)；實(shí)時(shí)熒光定量PCR（qRTPCR）法檢測IL-1β、IL-6、腫瘤壞死因子-α（TNF-α）的mRNA表達(dá)。結(jié)果 槲皮素脂質(zhì)體呈圓球狀，粒徑135nm，多分散系數(shù)0.260，電位（-4.28±0.66）mV。與模型組比較，槲皮素脂質(zhì)體20mg·kg^-1能顯著改善炎癥引發(fā)的肺部結(jié)構(gòu)變化，減輕免疫細(xì)胞浸潤肺組織導(dǎo)致的肺泡壁增厚和肺泡結(jié)構(gòu)紊亂，而槲皮素20mg·kg^-1沒有表現(xiàn)出治療效果；與模型組比較，槲皮素脂質(zhì)體20mg·kg^-1可顯著抑制肺組織成熟IL-1β蛋白表達(dá)（P＜0.01），顯著下調(diào)IL-1β、IL-6、TNF-α的mRNA表達(dá)（P＜0.01），而槲皮素20mg·kg^-1不具有抑制作用。結(jié)論 脂質(zhì)體制劑增強(qiáng)了槲皮素對(duì)小鼠肺部炎癥的抑制作用，減輕了LPS引起的肺組織損傷。

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

國家自然科學(xué)基金資助項(xiàng)目（81300059）