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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 王兆麟 | zh_TW |
| dc.contributor.advisor | Jaw-Ling Wang | en |
| dc.contributor.author | 戴薇庭 | zh_TW |
| dc.contributor.author | Wei-Ting Tai | en |
| dc.date.accessioned | 2025-02-19T16:39:09Z | - |
| dc.date.available | 2025-02-20 | - |
| dc.date.copyright | 2025-02-19 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2025-01-12 | - |
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Scientific Reports, 2016. 6(1): p. 29916. 68. Matta, A., et al., Molecular therapy for degenerative disc disease: clues from secretome analysis of the notochordal cell-rich nucleus pulposus. Scientific reports, 2017. 7(1): p. 45623. 69. Iwashina, T., et al., Low-intensity pulsed ultrasound stimulates cell proliferation and proteoglycan production in rabbit intervertebral disc cells cultured in alginate. Biomaterials, 2006. 27(3): p. 354-361. 70. Farnum, C.E. and N.J. Wilsman, Orientation of primary cilia of articular chondrocytes in three‐dimensional space. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, 2011. 294(3): p. 533-549. 71. Zeng, C., et al., Effectiveness of continuous and pulsed ultrasound for the management of knee osteoarthritis: a systematic review and network meta-analysis. Osteoarthritis and cartilage, 2014. 22(8): p. 1090-1099. 72. Horne, D., et al. Low intensity pulsed ultrasound (LIPUS) for the treatment of intervertebral disc degeneration. in Energy-based Treatment of Tissue and Assessment IX. 2017. SPIE. 73. Le Maitre, C.L., J.A. Hoyland, and A.J. Freemont, Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1β and TNFα expression profile. Arthritis research & therapy, 2007. 9: p. 1-11. 74. Wang, F., et al., Injectable hydrogel combined with nucleus pulposus‐derived mesenchymal stem cells for the treatment of degenerative intervertebral disc in rats. Stem cells international, 2019. 2019(1): p. 8496025. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/96587 | - |
| dc.description.abstract | 椎間盤的髓核退化經常伴隨著髓核細胞的形態改變，過度的機械負載被認為是導致這種現象的關鍵因素。為了更了解機械應力對於髓核細胞的影響，過去實驗室建立了三維培養之髓核細胞水膠穿刺模型，發現接近穿刺邊緣的髓核細胞核會受應力影響而拉長。基於這個現象，本研究欲探討髓核細胞核拉長現象由何種機械力敏感通道調控，並確認細胞核拉長現象所代表的生理意義。此外，本研究欲了解超音波介導的壓電刺激是否能夠逆轉髓核細胞核受力拉長之現象。最後，本研究欲建立小鼠體內的椎間盤退化模型，作為探討治療可行性的基礎。
本研究的結果表明，透過抑制ASIC3通道能夠抑制細胞核沿切線方向拉長之現象，然而抑制TRP4通道與Piezo1通道皆無法抑制此現象。此外，水膠穿刺模型中的細胞YAP螢光強度下降，且YAP定位在細胞核的比例亦下降。此現象將可能導致YAP下游與細胞修復相關的蛋白無法被轉譯。本研究還發現了微能量脈衝超音波介導之壓電刺激具有逆轉穿刺模型中髓核細胞核的拉長，且此現象不是由纖毛極性所調控。最後，本研究建立了鼠尾環椎間盤退化模型，此模型能用來探討超音波與壓電刺激對於椎間盤退化的治療可行性。總的來說，本研究有助於人們對於髓核細胞受力後的力生物學反應以及治療可行性有進一步的了解。 | zh_TW |
| dc.description.abstract | The degeneration of nucleus pulposus (NP) is often accompanied by morphological changes in NP cells, with excessive mechanical loading believed to be a key factor contributing to this phenomenon. To better understand the effect of mechanical stress on NP cells, the previous study in our lab established a three-dimensional hydrogel punctured model for NP cells culture, revealing that NP cells nuclei near the puncture edge elongate under stress. Based on this observation, this study aims to investigate which mechanosensitive channels regulate the elongation of NP cells nuclei and to determine the physiological significance of this elongation. Additionally, this study seeks to understand whether ultrasound-mediated piezoelectric stimulation can reverse the elongation of NP cells nuclei under stress. Finally, this study aims to establish an in vivo mouse model of intervertebral disc degeneration to explore the feasibility of potential treatments.
The results of this study indicate that inhibiting the ASIC3 channel can prevent the elongation of NP cells nucleus, whereas inhibiting the TRP4 and Piezo1 channels does not have this effect. Furthermore, the fluorescent intensity of YAP in cells within the hydrogel punctured model decreased. This phenomenon may lead to the failure of YAP downstream proteins associated with cell repair to be translated. The study also found that low-intensity pulsed ultrasound-mediated piezoelectric stimulation can reverse the elongation of NP cells nuclei in the puncture model, and this effect is not regulated by ciliary orientation. Lastly, a mouse tail-looping model was established, which can be used to investigate the therapeutic potential of ultrasound and piezoelectric stimulation for disc degeneration. Overall, this study contributes to a deeper understanding of the mechanobiological responses of NP cells to mechanical stress and the feasibility of potential treatments. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-02-19T16:39:09Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-02-19T16:39:09Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 致謝 II
摘要 III ABSTRACT IV 目次 V 圖次 VIII 第一章 緒論 1 1.1 臨床背景：下背痛 1 1.2 椎間盤簡介 1 1.2.1 髓核 2 1.2.2 纖維環 2 1.2.3 軟骨終板 2 1.3 椎間盤退化 2 1.4 機械力敏感通道 3 1.4.1 酸敏感離子通道（Acid-sensing ion channel, ASIC） 4 1.4.2 瞬時受體電位通道（Transient receptor potential channel, TRP） 4 1.4.3 壓電通道（Piezo channel） 5 1.5 YAP（YES-ASSOCIATED PROTEIN） 5 1.6 超音波簡介 6 1.6.1 超音波參數 6 1.6.2 聲強度（Intensity） 7 1.6.3 基本頻率（Fundamental frequency） 7 1.6.4 刺激時間（Duration） 8 1.6.5 佔空比（Duty cycle） 8 1.6.6 脈衝重現頻率（Pulse repetition frequency） 8 1.6.7 治療應用 8 1.7 壓電材料簡介 9 1.7.1 壓電在生醫上的應用 9 1.7.2 椎間盤中的壓電性質 10 1.8 初級纖毛 10 1.9 研究目的與重要性 10 第二章 材料與方法 12 2.1 髓核細胞培養 12 2.1.1 髓核細胞初代培養（Primary Culture） 12 2.1.2 髓核細胞的培養與繼代 13 2.2 水膠穿刺退化模型 14 2.2.1 水凝膠（Hydrogel）介紹 14 2.2.2 3D 水膠細胞培養環境之種植流程 14 2.2.3 水膠穿刺模型建立 15 2.3 水膠機械性質實驗 16 2.3.1 實驗設計 16 2.3.2 壓縮實驗儀器 17 2.3.3 分析方法 17 2.4 機械力敏感通道實驗 18 2.4.1 實驗設計 18 2.4.2 生物檢測法—免疫螢光染色 18 2.4.3 分析方法 20 2.4.3.1 細胞切線軸-法線軸長度比值（Nucleus elongation） 20 2.4.3.2 細胞核拉長個數比例（Incidence of nucleus elongation） 21 2.5 訊號傳遞實驗 21 2.5.1 實驗設計 21 2.5.2 生物檢測法—免疫螢光染色 22 2.6 超音波介導壓電刺激實驗 23 2.6.1 實驗設計 23 2.6.1.1 脈衝超音波介導壓電刺激實驗 23 2.6.1.2 連續超音波介導壓電刺激實驗 24 2.6.2 脈衝超音波刺激裝置 25 2.6.2.1 訊號產生器 25 2.6.2.2 功率放大器 25 2.6.2.3 超音波探頭與水桶 25 2.6.2.4 刺激裝置架設 26 2.6.2.5 能量量測 27 2.6.2.6 升溫情形量測 28 2.6.3 連續超音波刺激裝置 29 2.6.3.1 CelleX訊號產生器 29 2.6.3.2 Dish-LIC 29 2.6.3.3 刺激裝置架設 30 2.6.3.4 能量量測 30 2.6.3.5 升溫情形量測 31 2.6.4 生物檢測法—免疫螢光染色 32 2.6.5 分析方法 32 2.6.5.1細胞切線軸-法線軸長度比值（Nucleus elongation） 32 2.6.5.2 纖毛角度（Cilia orientation） 33 2.7 小鼠椎間盤退化模型建立實驗 33 2.7.1 鼠尾針刺模型（Stab injury model）[56] 33 2.7.2 鼠尾環模型（Tail-looping model）[57] 34 2.8 小鼠椎間盤退化治療實驗 35 2.8.1 實驗設計[58] 35 2.8.2 超音波與壓電治療裝置 36 2.8.2.1 訊號產生器 36 2.8.2.2功率放大器 36 2.8.2.3 陶瓷裸片 36 2.8.2.4 壓電薄膜 36 2.8.3治療裝置架設 37 2.8.4 能量量測 37 2.8.5 升溫情形量測 38 2.8.6 分析方法 39 2.9 統計檢定方法 40 第三章 實驗結果 41 3.1 前導實驗 41 3.1.1 水膠機械性質實驗結果 41 3.1.2 水膠穿刺退化模型建模結果 42 3.2 機械力敏感通道實驗結果 43 3.2.1 ASIC3通道抑制實驗 43 3.2.2 TRPV4通道抑制實驗 44 3.2.3 Piezo1通道抑制實驗 46 3.3 訊號傳遞實驗結果 47 3.4 超音波介導壓電刺激實驗結果 50 3.4.1 脈衝超音波介導壓電刺激實驗結果 50 3.4.2 連續超音波介導壓電刺激實驗結果 53 3.5 小鼠椎間盤退化模型建立實驗結果 55 3.5.1 鼠尾針刺模型 55 3.5.2 鼠尾環模型 56 3.6 小鼠椎間盤退化治療實驗結果 58 第四章 討論 60 4.1 機械力敏感通道實驗結果討論 60 4.2 訊號傳遞實驗結果討論 61 4.3 超音波介導壓電刺激實驗結果討論 61 4.4 小鼠椎間盤退化治療實驗結果討論 62 第五章 結論 64 第六章 未來展望 65 REFERENCE 66 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 椎間盤髓核細胞退化的力學模型與治療可行性探討 | zh_TW |
| dc.title | Mechanical Model and Therapeutic Feasibility Study of Nucleus Pulposus Degeneration | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-1 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 陳志成;徐善慧 | zh_TW |
| dc.contributor.oralexamcommittee | Chih-Cheng Chen;Shan-Hui Hsu | en |
| dc.subject.keyword | 椎間盤退化,髓核細胞,ASIC3,YAP,微能量超音波,壓電, | zh_TW |
| dc.subject.keyword | intervertebral disc degeneration,nucleus pulposus cell,ASIC3,YAP,low-intensity ultrasound,piezoelectricity, | en |
| dc.relation.page | 70 | - |
| dc.identifier.doi | 10.6342/NTU202403432 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-01-13 | - |
| dc.contributor.author-college | 工學院 | - |
| dc.contributor.author-dept | 醫學工程學系 | - |
| dc.date.embargo-lift | N/A | - |
| 顯示於系所單位： | 醫學工程學研究所 | |
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