| 研究生: |
高御豪 Kao, Yu-Hao |
|---|---|
| 論文名稱: |
紫杉醇藥物動力學對背根神經節神經元形態與黏彈性之影響 Effects of Paclitaxel Pharmacokinetics on Morphology and Viscoelasticity of Dorsal Root Ganglion Neurons |
| 指導教授: |
朱銘祥
Ju, Ming-Shaung |
| 學位類別: |
碩士 Master |
| 系所名稱: |
工學院 - 機械工程學系 Department of Mechanical Engineering |
| 論文出版年: | 2019 |
| 畢業學年度: | 107 |
| 語文別: | 中文 |
| 論文頁數: | 84 |
| 中文關鍵詞: | 化療引發之周邊神經病變 、紫杉醇藥物動力學 、細胞黏彈性力學 、原子力顯微鏡術 、免疫螢光顯微鏡術 |
| 外文關鍵詞: | chemotherapy-induced peripheral neuropathy, paclitaxel pharmacokinetics, cell viscoelasticity, atomic force microscopy, immunofluorescence |
| 相關次數: | 點閱:92 下載:0 |
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周邊神經病變是化學治療中常見之副作用,也是導致病患調降化療劑量的主因,採用降低副作用的治療方案能有效提升病人持續治療的意願。本研究以藥物動力學建立人體對紫杉醇的代謝模式,並以形貌與黏彈性力學評估3小時與24小時注射方案對小鼠背根神經節細胞造成影響的差異。兩個注射方案都觀察到細胞本體面積在療程的第24小時有上升的趨勢,Sholl profile則顯示神經細胞較快從3小時注射方案中恢復生長。螢光染色顯微鏡則觀察到神經細胞有軸突腫脹、微管退化與微管點狀分佈的現象。以原子力顯微鏡進行鬆弛試驗的結果顯示3小時注射方案會造成細胞本體內聚積較多的微管使視楊氏模數上升2倍。而24小時注射方案會造成細胞的彈性比下降,細胞的黏彈性質改變。本研究認為3小時注射方案會造成較多的微管聚積於細胞本體,但相比於24小時注射方案所需之恢復時間也較短,而24小時注射方案可能會對神經細胞造成不可逆之影響。
Paclitaxel is one of the chemotherapeutics that can induce the peripheral neuropathy of patients. The neuropathy is not only sensor-predominant but also the main reason for patients to withdraw from therapy. The goal of this in vitro study was to simulate the effects of two continuous intravenous infusion (CIV) plans on dorsal root ganglion (DRG) neurons via morphology and viscoelasticity of the neurons. The DRG neurons were separated into two experiment groups and treated with time-varying concentration of paclitaxel medium for 48 hours. Two series of step functions were utilized to approximate the concentration histories of the 3h and 24h CIV plans. The morphological images of selected DRG neurons were obtained every 24 hours for 48 hours by using an inverted microscope and extra samples were fixed for immunofluorescence imaging. The mechanical properties of living DRG neuronal soma were measured by an atomic force microscope at three timings, namely before the treatment, on peak concentration and a day after the peak concentration. The results revealed that the soma area of both 3h and 24h-CIV groups increased at 24 hours. The length of neuronal axons of 3h-CIV group increased with time, while those of 24h-CIV group remained at the same level between 24 hours and 48 hours. The soma apparent Young’s modulus increased for both groups. The elastic ratios of the 3h-CIV group decreased at the timing of peak concentration, while those of the 24h-CIV group decreased with time. In conclusions, the effects of paclitaxel on morphology and viscoelasticity for DRG neurons highly depend on the CIV protocol. The neurons treated with 3h-CIV may recover faster from the damage of paclitaxel.
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