中国组织工程研究

中国组织工程研究 ›› 2015, Vol. 19 ›› Issue (43): 6913-6917.doi: 10.3969/j.issn.2095-4344.2015.43.005

• 纳米生物材料 nanobiomaterials • 上一篇    下一篇

壳聚糖纳米粒包裹反义内皮素转换酶核酸表达质粒与哮喘气道高反应性

刘 佳   

  1. 解放军沈阳军区总医院呼吸内科，辽宁省沈阳市 110016
  • 收稿日期:2015-09-10 出版日期:2015-10-15 发布日期:2015-10-15
  • 作者简介:刘佳，女，1987年生，辽宁省沈阳市人，硕士，医师，主要从事哮喘研究。

Chitosan nanoparticles enfolding antisense endothelin converting enzyme RNA expression plasmid and airway hyperresponsiveness in asthmatic mouse models

Liu Jia   

  1. Department of Respiratory Medicine, General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, China
  • Received:2015-09-10 Online:2015-10-15 Published:2015-10-15
  • About author:Liu Jia, Master, Physician, Department of Respiratory Medicine, General Hospital of Shenyang Military Region, Shenyang 110016, Liaoning Province, China

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226

被引次数

4

摘要：

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。
 中国组织工程研究杂志出版内容重点：生物材料；骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性；组织工程

关键词: 生物材料, 纳米材料, 壳聚糖, 12-烷基化, 纳米粒, 内皮素转换酶, 哮喘, 小鼠, 气道高反应性

Abstract:

BACKGROUND: Studies have reported that under in 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 allergen.

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 saline via 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 cell culture supernatant were detected.
RESULTS AND CONCLUSION: Compared with the control group, the total number of plasmid cells, 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 all 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.
 

Key words: Chitosan, Nanoparticles, Asthma, Tissue Engineering