1] Department of Ultrasound, Xinqiao Hospital, The Third Military Medical University, Chongqing, China [2] Department of Ultrasound, 324th Military Hospital, Chongqing, China.
Gene Ther. 2013 Dec;20(12):1140-8. doi: 10.1038/gt.2013.41. Epub 2013 Aug 22.
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.
我们试图利用超声靶向阳离子脂质体载声敏微泡破坏基因传递系统来研究针对结缔组织生长因子（CTGF）的人工 microRNA（miRNA）的抗纤维化作用。阳离子脂质体通过生物素-亲和素系统与微泡结合。携带最有效的人工 miRNA 序列的质粒通过超声靶向阳离子脂质体载声敏微泡破坏基因传递系统传递给肝纤维化大鼠。结果表明，这种基因传递方法可有效地将质粒递送至大鼠肝脏。人工 miRNA 减少了肝纤维化的病理改变以及 CTGF 和转化生长因子β1 的蛋白和 mRNA 表达。此外，CTGF 基因沉默降低了 I 型胶原和α-平滑肌肌动蛋白的水平（P<0.01）。这些数据表明，使用超声靶向阳离子脂质体载声敏微泡破坏来递送针对 CTGF 的人工 miRNA 可能是改善肝纤维化的有效治疗方法。
