口服聚合微膠體投予脊髓神經保護基因
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。
In vivp oral neuroprotective genes delivery into mo use spinal cord by nano block biopolymeric micelle
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The treatment and repair of the spinal cord injury have been crucial subjec ts in recent years. In the past, MP was used to be treated with the acute spin al cord injury (SCI), though with great side effects.Recently research show s that after the spinal cord injury are very great relations of the demyelinati on with the death of oligodendrocyte cell and the damage of axon.
To obviate the multiple genetic mechanisms of MP, the anti-apoptotic prot ein 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), driv en by oligodendrcytes-specific promoters of Myelin basic protein(MBP) in to the spinal cord. Our finding indicate those two days after six doses of or al delivery of 40 μg with 3 times a day, gene expression was observed at 4 8 h in the spinal cord by immunohistological observation, Bcl-xL western- blotting, m RNA of Bcl-xL by real time PCR, Furthermore, using PM inco rporated with MP, we did observe the mRNA of Bcl-xL have sustained in t he spinal cord.
