標靶鈣離子通道調控及神經細胞生理現象之測試

Regulating cellular physiological phenomenon by targeting on calcium ion channel in neuronal cells

陳俐礽(Li-Reng Chen)

指導教授 ： 陳稷康 ； 陳冠宇

國立交通大學/資訊學院/生醫工程研究所/碩士(2018年)

摘要

神經系統在人體中扮演許多重要的角色，神經系統由眾多的神經元細胞構成，負責訊號傳遞，透過神經系統間彼此的訊息傳遞使生物能因應外界環境變化而作出適當的反應。因此當神經細胞受到損傷或是斷裂使得神經纖維受損，一般而言受到損傷的神經細胞會使用神經導管進行修復並在施加適當的電刺激。本研究最主要目的為希望藉由神經細胞的生理現象，運用鈣離子能夠協助神經細胞訊號傳遞之原理，建立一套系統協助治療神經細胞訊號傳遞。離子通道是一種成孔蛋白，透過不同屬性的離子通道能夠使特定的離子進出細胞膜，其中鈣離子通道是近年研究熱門的離子通道，離子通道調節許多生理機制，像是心肌跳動、神經系統的訊號傳遞等，都與鈣離子流動進出細胞之間有很大的關聯。
在此我們使用轉染技術將鈣離子通道轉染至細胞上，促使鈣離子能夠在細胞內外流動，並且搭配修飾上抗體的磁性奈米鐵粒子，達到標靶的目的。磁性奈米鐵粒子(Iron Oxide Nanoparticles, Fe3O4) 帶有超順磁性而極易將其以外加磁場的方式來達到各種生醫領域的運用，像是癌症的標靶藥物治療、血液中使用磁性粒子進行的分析檢測、核磁共振診斷疾病以及在癌症治療作為高熱試劑。磁性奈米鐵粒子能夠藉由表現修飾上抗體等蛋白質，配合抗原和抗體間結合來補抓特定蛋白的原理，可使磁性奈米鐵粒子更具標靶性，使其應用性更加廣泛。並使用外加磁場磁升溫原理激活離子通道開關，目前已證實磁場升溫不會造成顯著的細胞死亡，後續實驗將使用磁性奈米鐵粒子標靶於離子通道上。
基於上述理論我們將設計一套生物奈米技術的系統，藉由磁性奈米鐵粒子修飾以及外加磁場調控鈣離子通道，誘導神經細胞發生鈣離子流動使訊息流動，協助神經細胞訊號傳遞並且在未來可以應用於輔助神經治療。

關鍵字

神經細胞 ； 鈣離子通道 ； 磁場 ； 磁性奈米粒子

並列摘要

The nervous system plays many important roles in the human body. The nervous system is composed of numerous neuronal cells and is responsible for signal transmission.Through the communication between the nervous systems, the bio-energy can respond appropriately to changes in the external environment. Therefore, when the nerve cells are damaged or broken, the nerve fibers are damaged. In general, damaged nerve cells are repaired using a nerve conduit and are subjected to appropriate electrical stimulation. The main purpose of this study is to establish a system to assist in the treatment of nerve cell signal transmission by using the physiological phenomenon of nerve cells and using calcium ions to assist in the transmission of nerve cells. The ion channel is a pore-forming protein that allows specific ions to enter and exit the cell membrane through ion channels of different properties. Among them, calcium channel is a popular ion channel in recent years. The ion channel regulates many physiological mechanisms, such as myocardial beating and nervous system signals. Transmission, etc., are strongly related to the flow of calcium ions into and out of the cell.
Here we use transfection technology to transfect calcium channels into cells, allowing calcium ions to flow inside and outside the cell, and with magnetic nano-iron particles modified with antibodies to achieve the target. Iron Oxide Nanoparticles (Fe3O4) are superparamagnetic and can be easily applied to various biomedical fields, such as cancer drug target treatment and magnetic particles in blood. Analytical tests performed, nuclear magnetic resonance diagnosis of diseases, and treatment of cancer as a hyperthermia reagent. The magnetic iron oxide nanoparticles can make the magnetic iron oxide nanoparticles more target by using a protein such as a modified antibody and a combination of an antigen and an antibody to complement the specific protein, thereby making the application more widely. The ion channel switch is activated by the magnetic field heating principle of the external magnetic field. It has been confirmed that the magnetic field heating does not cause significant cell death, and subsequent experiments will use magnetic iron oxide nanoparticles to target the ion channel.
Based on the above theory, we will design a system of bio-nano technology, which uses magnetic magnetic iron oxide nanoparticles to modify and external magnetic field to regulate calcium channel, induces calcium ions to flow in nerve cells, and helps the nerve cells to transmit signals and can be applied to assisted neuron therapy in the future.

並列關鍵字

neuron cell ； ion channel(TRPV1) ； magnetic field ； magnetic nanoparticles

參考文獻

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