脂质微泡介导转染MIF siRNA对小鼠急性肺损伤的保护作用

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (7): 737-741.

脂质微泡介导转染MIF siRNA对小鼠急性肺损伤的保护作用

江永南^1,2, 莫红缨³, 陈建海¹

¹南方医科大学南方医院药学部,广州 510515,广东;
²广东食品药品职业学院,广州 510520,广东;
³广州医学院第一附属医院呼吸疾病国家重点实验室,广州 510120,广东

收稿日期:2010-05-04 修回日期:2010-06-27 出版日期:2010-07-26 发布日期:2020-09-15
通讯作者: 陈建海,男,研究方向:非病毒基因载体的研制及基因给药系统。Tel: 020-61642173 E-mail: jhchen06@126.com
作者简介:江永南,男,博士生,副教授,研究方向:基因载体合成与转染系统研究。Tel: 020-28854860 E-mail: jynsnake@tom.com
基金资助:
国家自然科学基金项目(30772660)

Protective effect of MIF siRNA mediated by lipid microbubbles on acute lung injury in mice

JIANG Yong-nan^1,2, MO Hong-ying³, CHEN Jian-hai¹

¹Department of Pharmacy, Nanfang Hospital, Southern Medical University Guangzhou 510515,Guangdong, China;
²Guangdong Food and Drug Vocational College, Guangzhou 510520,Guangdong,China;
³State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120,Guangdong,China

Received:2010-05-04 Revised:2010-06-27 Online:2010-07-26 Published:2020-09-15

摘要/Abstract

摘要： 目的: 通过探讨超声微泡基因转染系统转染MIF siRNA对小鼠急性肺损伤的保护作用,评价超声微泡基因转染系统的有效性。方法: 以脂多糖(LPS)诱导小鼠建立急性肺损伤动物模型,随机分成4组:正常对照组(Con)、LPS刺激组(LPS)、LPS+PC+MIF siRNA治疗组(PC+MIF siRNA)、LPS+WP+MIF siRNA治疗组(WP+MIF siRNA);通过超声微泡基因转染系统转染MIF siRNA,运用EMSA、Western-Blot、ELISA和相关病理检测技术,观察小鼠肺组织NF-κB/ IκB-α表达、炎症介质TNF-α、IL-1β、IL-6水平,及肺组织湿干重比和炎症病理病变,探讨MIF siRNA对小鼠急性肺损伤的保护作用。结果: WP+MIF siRNA治疗组通过上调肺组织细胞浆中IκB-α表达,对LPS刺激激活的细胞核NF-κB有明显抑制作用、从而抑制炎症介质TNF-α、IL-1β、IL-6释放,减轻小鼠肺组织病理损伤。但PC+MIF siRNA治疗组对LPS刺激导致的小鼠肺损伤无任何改善的治疗作用。结论: 脂质微泡/PEI-Chol介导的基因转染系统能有效转染MIF siRNA,对LPS介导的小鼠急性肺损伤具有一定的保护作用。

关键词: 脂质微泡, MIF siRNA, 急性肺损伤

Abstract: AIM: To investigate the protective effect of MIF siRNA mediated by ultrasound lipid microbubbles gene transfer system and evaluate the efficacy of this gene transfer system.METHODS: The model of acute lung injury was induced by LPS in mice which were randomly divided into 4 groups: normal control group (Con), LPS stimulation (LPS), LPS + PC + MIF siRNA treatment group (PC + MIF siRNA), LPS + WP + MIF siRNA treatment group (WP + MIF siRNA). The MIF siRNA was transfected by microbubbles ultrasound. These methods including EMSA, Western-Blot, ELISA and HE stained for histopathological examination were used to observe the expressions of NF-κB and IκB-α, to detect the levels of inflammatory mediators of TNF-α, IL-1β, IL-6, and to assess the pathological changes.RESULTS: MIF siRNA was carried and transferred by WP + MIF siRNA which up-regulated the expression of IκB-α in cytoplasm and significantly inhibited the expression of NF-κB in nucleus, then inhibited the levels of inflammatory mediators of TNF-α, IL-1β, IL -6 and improved the pathological changes. But the PC+ MIF siRNA treatment group has no any improvement on acute lung injury in mice.CONCLUSION: MIF siRNA can be effectively transferred by lipid microbubbles gene transfer system and have protective effect on acute lung injury in mice.

Key words: Lipid microbubbles, MIF siRNA, Acute lung injury

中图分类号:

R965

江永南, 莫红缨, 陈建海. 脂质微泡介导转染MIF siRNA对小鼠急性肺损伤的保护作用[J]. 中国临床药理学与治疗学, 2010, 15(7): 737-741.

JIANG Yong-nan, MO Hong-ying, CHEN Jian-hai. Protective effect of MIF siRNA mediated by lipid microbubbles on acute lung injury in mice[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(7): 737-741.

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