J052012 ソノポレーション法とチャネル遺伝子を用いた末梢循環障害の新規治療法の確立作成について([J05201]ドラッグデリバリーシステムでの流動現象とデバイス開発(1))

Abstract

The combination of ultrasound and nano-bubbles coated with lipid bilayers (i.e. hybrid nano-bubbles) induces transient membrane permeability, leading to direct delivery of exogenous molecules (such as plasmid, siRNA, panticancer drugs, proteins etc.) into cells with minimal invasiveness. This method is generally termed `sonoporation' in drug delivery systems parlance. When Kir6.2 genes have transfected into native smooth muscle layers of mouse aorta by use of sonoporation, RT-PCR analysis revealed the expression of Kir6.2 transcripts in vascular smooth muscle. When Kir6.2 genes, tagging with Myc-genes, were transfected into native smooth muscle layers using sonoporation, immunohistochemical studies have revealed that Kir6.2 and Myc proteins were co-expressed in vascular smooth muscle cells. The phenylephrine-induced contraction of mouse aorta was significantly reduced after the treatment of Kir6.2 gene-sonoporation, hyperpolaring the membrane potentials. These results suggest that Kir6.2 genes were functionally expressed in mouse vascular smooth muscles, causing a vascular relaxation due to the activity of Kir6.2.