口服聚合微膠體投予脊髓神經保護基因
In vivp oral neuroprotective genes delivery into mouse spinal cord by nano block biopolymeric micelles
中文摘要
脊髓損傷後的照顧和修復一直是近年來急欲研究的課題。雖然過去的方法皆以藥 物 Methyprednisolone (MP) 來控制和治療，但是人們卻發現這樣的方法會造成 較大之副作用。然而在過去的研究中顯示，脊髓損傷後,去髓鞘化與寡突狀細胞
的死亡和軸索的傷害有很大的關係。因此，本實驗主要目的針對BCL-xL ，一與
抑制寡突狀細胞壞死之相關性基因，和利用一段可以專一性表現在寡突狀細胞 的啟動子MBP (myelin basic protein)做為標的基因，且利用 polymeric Micelle (PM) 進行基因傳遞的方式架構出一個質體 DNA (pMBP-Bcl-xL-EGFP)來進行基 因治療評估。同時也觀察在給予 MP 的治療劑量下，同時觀察 Bcl-xL 之抗細胞 壞死的基因表現量。在初步結果發現中，直接從脊髓組織之螢光的表現 EGFP 或 是從Bcl-xL 蛋白質西方點墨法的或是由 mRNA Bcl-xL 定量 Real-time PCR ，質 體DNA 是可以在口服六個 dose 下，48 小時後有其表現。而在給予 MP 的實驗中 我們也發現到，有 PM 包覆的 MP 和在 mRNA 的 Bcl-xL 與，似乎有延長作用時 間的效果。
英文摘要
The treatment and repair of the spinal cord injury have been crucial subjects in recent years. In the past, MP was used to be treated with the acute spinal cord injury (SCI), though with great side effects.Recently research shows that after the spinal cord injury are very great relations of the demyelination with the death of oligodendrocyte cell and the damage of axon.
To obviate the multiple genetic mechanisms of MP, the anti-apoptotic protein Bcl-xL gene could be one approvals of developing novel gene delivery systems to avoid the advance side of effect of MP.
We have a nano-size of PM with Bcl-xL gene (pMBP-Bcl-xL-EGFP), driven by oligodendrcytes-specific promoters of Myelin basic protein(MBP) into the spinal cord. Our finding indicate those two days after six doses of oral delivery of 40 μg with 3 times a day, gene expression was observed at 48 h in the spinal cord by immunohistological observation, Bcl-xL western-blotting, m RNA of Bcl-xL by real time PCR, Furthermore, using PM incorporated with MP, we did observe the mRNA of Bcl-xL have sustained in the spinal cord.
