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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 王兆麟 | zh_TW |
dc.contributor.advisor | Jaw-Lin Wang | en |
dc.contributor.author | 吳觀宇 | zh_TW |
dc.contributor.author | Guan-Yu Wu | en |
dc.date.accessioned | 2023-08-09T16:07:13Z | - |
dc.date.available | 2023-11-18 | - |
dc.date.copyright | 2023-08-09 | - |
dc.date.issued | 2023 | - |
dc.date.submitted | 2023-07-24 | - |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/88231 | - |
dc.description.abstract | 多項文獻的實驗結果已經證實,低強度超音波具備高空間解析度與深度傳播的能力,進而促進神經調節。雖然低強度超音波已為神經刺激的臨床診斷帶來新的方法;但是對於超音波在分子生物層面作用的力學機制,尚未有明確的解釋。本研究開發一種特殊的超音波刺激裝置:超音波微管,刺激背根神經元和小鼠神經纖維瘤細胞;並詳細研究細胞受到超音波刺激後,產生鈣離子反應相關的離子通道。玻璃微管的針尖呈現閉口的狀態;作為一個波傳導的裝置,將超音波傳感器發射的超音波傳導至針尖,再經由針尖釋放機械力刺激。當超音波被釋放時,會產生兩種力學刺激:第一種是聲壓,其會對行進方向上的細胞產生擠壓的效應;第二種是聲流,其會對細胞膜表面施加橫向的作用力,稱為剪力。這兩種力量的量值可以經由超音波參數:輸入電壓與佔空比的組合(模組)進行調控。
本研究的實驗結果證實,酸敏感離子通道一型1a(Acid-sensing ion channels 1a, 簡稱ASIC1a)在背根神經元和小鼠神經纖維瘤受超音波刺激所產生的鈣離子反應中,扮演了機械力敏感通道的角色;另外本研究特別使用ASIC1a基因修飾的老鼠進行實驗,也證實了同一個實驗結果。除此之外,本研究剔除本體感覺神經元上的酸敏感離子通道三型基因(ASIC3),發現鈣離子反應的程度會受到影響,證實ASIC3可能是本體感覺神經元上的機械力敏感通道。最後,本研究發現比起聲壓主導的超音波刺激,聲流主導刺激更容易造成細胞的鈣離子濃度變化。 | zh_TW |
dc.description.abstract | Lines of compelling evidence have shown that low-intensity ultrasound has the capability of neuromodulation modality with exquisite spatial specificity and depth penetration. Although low-intensity focused ultrasound holds great promise as a novel approach to the potential clinical applications of neuron stimulation, the underlying mechanism at the cellular and molecular level remain unclear. In this study, we utilized a device of micropipette-guided ultrasound to dissect the involved channels in ultrasound-induced activation of somatosensory neurons and neuroblastoma Neuro-2a cells. The glass micropipette with an end-closed tip is a developed wave-guide device to transport the force of ultrasound. Ultrasound from the tip generates two forms of force: one is the acoustic pressure into cell solution with acoustic pressure exerting on cells placed along its path, and the other is the streaming flow applying shear force on cells. These two force modalities could be fine-tuned by the input voltage and the duty factor. Our results demonstrated ASIC1a has been identified as a vital mechanosensitive channel to mediate low-intensity ultrasound-induced activation of dorsal root ganglion neurons and Neuro-2a cells. We further generated a transgenic mice and probe the role of ASIC1a in ultrasound-sensitive calcium response. In addition, ASIC3 is expressed in proprioceptors so that we generated transgenic mice with a floxed allele of ASIC3 (ASIC3f/f) and probed ASIC3 also has been a mechanoreceptor. Lastly, our results confirmed streaming force dominantly modulate intracellular calcium concentration compared to compressional predominant force. | en |
dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2023-08-09T16:07:13Z No. of bitstreams: 0 | en |
dc.description.provenance | Made available in DSpace on 2023-08-09T16:07:13Z (GMT). No. of bitstreams: 0 | en |
dc.description.tableofcontents | 口試委員會審定書 i
致謝 ii 中文摘要 iv Abstract v 目 錄 vi 圖目錄 x 表目錄 xviii 符號與術語縮寫索引 xix 第一章 緒論 1 1-1 研究背景 1 1-1-1 機械力敏感通道之研究背景 1 1-1-2 超音波微管開發之研究背景 5 1-1-3 酸敏感離子通道一型受超音波刺激之研究背景 7 1-1-4 酸敏離子通道三型受力學刺激之研究背景 9 1-1-5 研究背景總結 11 1-2 問題與研究目的 12 1-3 研究架構 14 1-4 研究範圍 17 1-5 研究限制 18 第二章 文獻回顧 19 2-1 波動力學與聲學簡介 19 2-1-1 從波動力學方程式推導聲強度計算之理論研究 20 2-1-2 聲波的基本性質 26 2-2-3 聲阻抗的基本性質 28 2-2-4 聲強度 30 2-2-5 聲強級 31 2-2 波傳導的種類 32 2-2-1 縱波與橫波 32 2-2-2 板波 34 2-2-3 洩漏蘭姆波 39 2-3 超音波造成的物理效應簡介 40 2-3-1 基本性質 40 2-3-2 超音波參數定義 43 2-3-3 聲壓(聲輻射力) 45 2-3-4 聲流 46 2-3-5 空蝕效應 47 2-3 壓電效應原理簡介 49 第三章 研究方法 51 3-1 實驗設備 51 3-1-1 實驗設備總體架設 51 3-1-2 訊號產生器與放大器 54 3-1-3 超音波探頭與玻璃微管 56 3-1-4 溶液置換系統 58 3-1-5 鈣離子影像顯微鏡 60 3-2 使用細胞與材料 62 3-2-1 小鼠神經纖維瘤細胞 62 3-2-2 背根神經節細胞 63 3-2-3 漢克平衡酸鹼緩衝溶液 63 3-2-4 Fura-2/AM 鈣離子螢光染劑 65 3-3 鈣離子影像分析方法 65 第四章 實驗設計 68 4-1 超音波微管之機械性質探討與量測 68 4-1-1 超音波聲壓量測實驗規劃 68 4-1-2 超音波聲流場剪應力量測實驗規劃 76 4-2 實驗一:小鼠神經纖維瘤細胞之鈣離子反應探討 78 4-2-1 超音波微管刺激方法的制定 80 4-2-2 檢驗離子通道類型之實驗方法的制定 81 4-3 實驗二:背根神經節細胞之鈣離子反應探討 84 4-4 實驗三:本體感覺神經元之鈣離子反應探討 86 4-5 實驗四:聲壓與聲流對鈣離子反應影響之比較 88 第五章 實驗結果 89 5-1 超音波微管之機械性質量測結果 89 5-1-1 聲壓量測結果 89 5-1-2 聲流量測結果 95 5-2 小鼠神經纖維瘤細胞之鈣離子反應實驗結果 103 5-2-1 N2a細胞受超音波模組刺激之反應結果 103 5-2-2 超音波微管刺激方法的制定實驗結果 105 5-2-3 離子通道抑制劑檢驗N2a細胞離子通道實驗結果 108 5-3 背根神經節細胞之鈣離子反應實驗結果 111 5-4 本體感覺神經元之鈣離子反應實驗結果 114 5-5 聲壓與聲流對鈣離子反應之影響實驗結果 116 第六章 結論與未來展望 119 6-1 結論 119 6-2 討論與未來展望 120 參考資料 121 | - |
dc.language.iso | zh_TW | - |
dc.title | 探究不同力學模組的超音波刺激對機械力敏感通道所引發的鈣離子反應之影響 | zh_TW |
dc.title | The Cellular Calcium Response to the Ultrasound Stimulation with Specific Force Modalities via Mechanosensitive Receptors | en |
dc.type | Thesis | - |
dc.date.schoolyear | 111-2 | - |
dc.description.degree | 碩士 | - |
dc.contributor.oralexamcommittee | 李百祺;陳文翔;陳志成 | zh_TW |
dc.contributor.oralexamcommittee | Pai-Chi Li;Wen-Shiang Chen;Chih-Cheng Chen | en |
dc.subject.keyword | 導波,低強度超音波,機械力敏感通道,酸敏感離子通道一型,酸敏感離子通道三型, | zh_TW |
dc.subject.keyword | Guided wave,Low-intensity ultrasound,Mechanoreceptors,ASIC1a,ASIC3, | en |
dc.relation.page | 125 | - |
dc.identifier.doi | 10.6342/NTU202301318 | - |
dc.rights.note | 同意授權(全球公開) | - |
dc.date.accepted | 2023-07-25 | - |
dc.contributor.author-college | 工學院 | - |
dc.contributor.author-dept | 醫學工程學系 | - |
顯示於系所單位: | 醫學工程學研究所 |
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