BACKGROUND:Studies have reported that underin vitro experimental environment, antisense endothelin nucleic acid nanometer carrier can express target nucleic acid and produce RNA interference effect after enfolding by 12-alkylated chitosan nanoparticles, which can effectively inhibit the excessive generation of endothelin from inflammatory cytokines induced by alergen. OBJECTIVE:To investigate the effect of 12-alkylated chitosan nanoparticles enfolding antisense endothelin converting enzyme RNA expression plasmid on airway hyperresponsiveness in asthmatic mouse models. METHODS: Forty Balb/c mice were randomly divided into four groups: control, chitosan nanoparticles, normal saline and plasmid groups. Mice in the chitosan nanoparticles, normal saline and plasmid groups were subjected to sensitization by an intraperitoneal injection with ovalbumin (0, 14 days) and motivation by aerosol inhalation of ovalbumin (24, 25, 26 days) to induce asthma models. Mice in the control group were subjected to sensitization and motivation by the perfusion of normal saline. At 24hours before the first excitation, mice in the control, chitosan nanoparticles, normal saline and plasmid groups were perfused with normal salinevia airway, 12-alkylated chitosan nanoparticles, normal saline and antisense endothelin converting enzyme RNA. At 48 hours after the last excitation, the airway reactivity of mice was detected. After 28 days, bronchoalveolar lavage fluid cytology, lung histopathology, cytokines in spleen cel culture supernatant were detected. RESULTS AND CONCLUSION:Compared with the control group, the total number of plasmid cels, the percentage of eosinophils, eosinophil absolute counts, interleukin-4 levels, endothelin levels and airway hyperresponsiveness of mice in chitosan nanoparticles, normal saline and plasmid groups were increased (P < 0.05), and the lung inflammation was more severe. These indicators in the chitosan nanoparticles group were al lower than those in the normal saline and plasmid groups (P < 0.05) and the degree of inflammation was lighter than that in the saline and plasmid groups. These results demonstrate that 12-alkylated chitosan nanoparticles enfolding antisense endothelin converting enzyme RNA expression plasmid can reduce the synthetic amount of asthma endothelin and inhibit airway responsiveness.%背景：有研究报道体外实验环境下，反义内皮素核酸纳米载体经12-烷基化壳聚糖纳米粒包裹之后可以表达目标核酸，产生RNA干扰效应，达到有效抑制变应原诱导炎症因子内皮素过度生成的效果。目的：观察12-烷基化壳聚糖纳米粒包裹反义内皮素转换酶核酸表达质粒对哮喘模型小鼠气道高反应性的影响。方法：将40只Balb/c小鼠随机均分为4组，壳聚糖纳米组、生理盐水组及质粒组腹腔注射卵清蛋白致敏(0，14 d)、雾化吸入卵清蛋白激发(24，25，26 d)，诱导哮喘模型；对照组给予生理盐水致敏、激发。首次激发前24 h，对照组、壳聚糖纳米组、生理盐水组、质粒组分别经气道灌注生理盐水、包裹反义内皮素转换酶核酸的12-烷基化壳聚糖纳米粒、生理盐水及反义内皮素转换酶核酸。末次激发后48 h，检测小鼠气道反应性；28 d后，进行支气管肺泡灌洗液细胞学、肺组织病理学、脾细胞培养上清液细胞因子检测。结果与结论：与对照组比较，壳聚糖纳米组、生理盐水组、质粒组细胞总数、嗜酸性粒细胞百分比、嗜酸性粒细胞绝对计数、白细胞介素4水平、内皮素水平及气道反应性均升高(P<0.05)，肺部炎症程度较重；壳聚糖纳米组上述指标均低于生理盐水组、质粒组(P<0.05)，炎症程度轻于生理盐水组、质粒组。表明12-烷基化壳聚糖纳米粒包裹反义内皮素转换酶核酸表达质粒可降低哮喘内皮素合成量，抑制气道高反应性。
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