利用超声和阳离子脂质体息微泡与人工微RNA抑制肝纤维化

StephenW

Gene Therapy (2013) 20, 1140–1148; doi:10.1038/gt.2013.41; published online 22 August 2013

        Inhibition of hepatic fibrosis with artificial microRNA using ultrasound and cationic liposome-bearing microbubbles

D Yang1,2,4, Y-H Gao1,4, K-B Tan1, Z-X Zuo1, W-X Yang1, X Hua3, P-J Li1, Y Zhang1 and G Wang1

• 1Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China
• 2Department of Ultrasound, 324th Military Hospital, Chongqing, China
• 3Department of Ultrasound, Southwest Hospital, The Third Military Medical University, Chongqing, China
  

Correspondence: Professor K-B Tan, Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, No.183 Xinqiao Street, Chongqing 400037, China. E-mail: [email protected]

4These authors contributed equally to this work.

Received 6 November 2012; Revised 10 June 2013; Accepted 12 June 2013
Advance online publication 22 August 2013

Top of pageAbstract

We sought to investigate the antifibrotic effects of an artificial microRNA (miRNA) targeting connective tissue growth factor (CTGF) using the ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system. Cationic liposomes were conjugated with microbubbles using a biotin–avidin system. Plasmids carrying the most effective artificial miRNA sequences were delivered by ultrasound-targeted cationic liposome-bearing microbubble destruction gene delivery system to rats with hepatic fibrosis. The results show that this method of gene delivery effectively transported the plasmids to the rat liver. The artificial miRNA reduced hepatic fibrosis pathological alterations as well as the protein and mRNA expressions of CTGF and transforming growth factor β1. Furthermore, the CTGF gene silencing decreased the levels of type I collagen and α-smooth muscle actin (P<0.01). These data suggest that delivery of an artificial miRNA targeted against CTGF using ultrasound-targeted cationic liposome-bearing microbubble destruction may be an efficacious therapeutic method to ameliorate hepatic fibrosis.

Keywords:

artificial microRNA; connective tissue growth factor; gene delivery; hepatic fibrosis; ultrasound; microbubble

StephenW

基因治疗（ 2013年） 20 ， 1140年至1148年， DOI ： 10.1038/gt.2013.41 ;网上公布2013年8月22日
利用超声和阳离子脂质体息微泡肝纤维化与人工微RNA的抑制

ð阳1 ， 2,4 ， YH Gao1 ， 4 KB TAN1 ， ZX Zuo1 ， WX洋1 ，X Hua3 ， PJ莉，Y张屹和G Wang1

    超声，新桥医院，第三军医大学，重庆，中国的教研室
    教研室超声，第324军医院，重庆，中国
    超声，西南医院，第三军医大学，重庆，中国的3Department

通讯： KB陈教授，第三军医大学，中国超声科，新桥医院，新桥183号街，重庆400037 。电子邮件： [email protected]

4These同等贡献这项工作。

收到2012年11月6日，经修订的2013年6月10日，接受2013年6月12日
提前在网上公布2013年8月22日

摘要

我们试图用超声靶向阳离子脂质体息破坏微泡基因传递系统靶向结缔组织生长因子（CTGF ）调查的人工微RNA （ miRNA）的抗纤维化作用。阳离子脂质体缀合使用生物素 - 亲和素系统的微泡。质粒携带最有效的人工miRNA序列是由超声靶向阳离子脂质体息破坏微泡基因传递系统交付给大鼠肝纤维化。结果表明，基因递送的这种方法有效地输送的质粒的大鼠肝。人工miRNA的降低肝纤维化的病理改变以及结缔组织生长因子蛋白和mRNA的表达和转化生长因子β1 。此外， CTGF基因沉默下降型的电平I型胶原和α-平滑肌肌动蛋白（P <0.01）。这些数据表明，递送靶向CTGF使用超声靶向阳离子脂质体息微泡的人工miRNA的可能是有效的治疗方法来改善肝纤维化。
关键词：

人工微RNA ;结缔组织生长因子;基因传递;肝纤维化;超声;微泡