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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳志成(Chih-Cheng Chen) | |
dc.contributor.author | Yitin Yen | en |
dc.contributor.author | 顏怡庭 | zh_TW |
dc.date.accessioned | 2021-06-13T00:11:18Z | - |
dc.date.available | 2008-07-30 | |
dc.date.copyright | 2007-07-30 | |
dc.date.issued | 2007 | |
dc.date.submitted | 2007-07-26 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/28537 | - |
dc.description.abstract | 發炎反應是身體為了對抗外來傷害性刺激、啟動修復功能所引發的保護機制。發炎時,身體組織受到傷害而使細胞內物質流出,其中的氫離子和酸性代謝物常造成組織酸化。疼痛過敏化的現象也常伴隨發炎反應出現。疼痛過敏化所描述的現象是,在平常會造成痛覺的刺激下,疼痛的感覺或反應被放大。神經上離子通道的活化或是表現量的上升,都有可能是疼痛過敏化的機制。其中,痛覺神經上的第三型酸離子接受器(ASIC3)會因pH值下降而被活化,暗示了它在疼痛過敏化的發生上所扮演的角色。
當ASIC3基因被剔除,我們期望會看到動物對於疼痛的敏感度下降,但是小鼠在不同的痛覺研究模式下,反應非常的多樣化。在此,我將對於不同藥物所引發的發炎反應以及伴隨而來的疼痛過敏化現象作一有系統的研究,比較野生型和ASIC3剔除小鼠的差異來推論ASIC3所扮演的角色。佛氏佐劑和鹿角膠是兩種常見的發炎引發物,在此實驗中我在小鼠的後腳掌或腓腸肌分別施打這些藥物,之後利用同步定量聚合連鎖反應來測定ASIC3及其他離子通道是否伴隨發炎反應調節基因的表現量,同時檢驗發炎反應對組織造成的傷害。這些變化都需要行為上的實驗來支持他們所代表的現象是有功能上的意義的,因此可以表徵疼痛過敏化的行為實驗也必須進行。 在我的論文研究中發現,機械性或是熱學性疼痛過敏化的發生皆需要ASIC3的存在。這些痛覺感受的改變,可能是因為ASIC3透過活化導致了一些發炎反應的變化,例如神經肽的分泌,而引響了調控機制複雜的免疫反應改變,進而引起肉芽腫或血管炎的生成。另一個可能是ASIC3的存在可以調節鈉離子通道Nav1.9的表現,透過Nav1.9來調節發炎反應時熱學性疼痛過敏化的生成及維持。 | zh_TW |
dc.description.abstract | Inflammation is a tightly regulated response of body tissues to noxious stimuli as a means to remove the irritant and to heal. During inflammation, damage to the body often causes tissue acidosis accompanied by hyperalgesia. Hyperalgesia is an increased response to a stimulus, which is normally painful. Ion channel activation or up-regulation underlies the cellular mechanism of hyperalgesia. Acid-sensing ion channel 3 (ASIC3) on nociceptive neurons is activated by the increase of proton concentrations, implying its role in the process of hyperalgesia development.
The disruption of ASIC3 was expected to lower the animals' pain response to noxious stimuli, but ASIC3 knockout mice showed diverse responses under different pain paradigms. In this thesis, a systematic study of hyperalgesia induced by different inflammatory agents was conducted, and the results were compared between wild-type mice and ASIC3 knockouts. Complete Freund’s adjuvant or carrageenan was injected into the plantar surface of the hind paw (cutaneous inflammation) or the gastrocnemius muscle (deep-tissue inflammation). Real-time PCR was performed to quantify gene regulation of ASIC3 and other ion channels during inflammatory states. Pathological examination was carried out to determine the effect of inflammation. Behavioral changes in the response to noxious stimuli during inflammation were tested to characterize the development of hyperalgesia. In this study, both mechanical and thermal hyperalgesia seemed to be AISC3-dependent. This could be correlated with the different inflammatory responses mediated by ASIC3, where ASIC3 influenced the down-stream network of immune response to trauma by mediating neuropeptide release which resulted in granuloma formation and vasculitis development. The development of mechanical and thermal hyperalgesia may also be correlated with ASIC3-dependent Nav1.9 up-regulation, which contributes to thermal hyperalgesia in inflammatory states. | en |
dc.description.provenance | Made available in DSpace on 2021-06-13T00:11:18Z (GMT). No. of bitstreams: 1 ntu-96-R94b41005-1.pdf: 11454614 bytes, checksum: ac77791a91f574debb6e9a75291192f4 (MD5) Previous issue date: 2007 | en |
dc.description.tableofcontents | 口試委員審定書……………………………………………………ⅰ
Acknowledgement……………………………………………………ⅱ 中文摘要……………………………………………………ⅲ Abstract……………………………………………………ⅳ Table of Contents……………………………………………………ⅵ List of Figures……………………………………………………ⅸ List of Tables……………………………………………………ⅹ Chapter1:Introduction……………………………………………………....1 Chapter 2: Material and Methods………………………….....5 2.1 Induction of inflammation…………………………….....5 2.2 Assessment of thermal and mechanical sensitivity....5 2.2.1 Von Frey filaments test……………………………..6 2.2.2 Radiant heat test……………………………………..6 2.3. Pathological examination………………………………...6 2.3.1 Evaluation of paw edema……………………………..7 2.3.2 Histological examinations…………………………..7 2.3.3 Immunohistochemistry………………………………….7 2.3.4 Quantifying the severity of vasculitis………...7 2.3.5 Granuloma density…………………………………....8 2.4 Determination of gene expression level in dorsal root ganglia………...........................................8 2.4.1 DRG isolation………………………………………....8 2.4.2 RNA extraction………………………………………….8 2.4.3 Reverse transcription…………………………………9 2.4.4 Quantitative real-time PCR………………………….9 2.5 Statistical analysis……………………………………….10 Chapter 3: Result………………………………………………..11 3.1 Behavior tests……………………………………………….11 3.1.1 Paw withdrawal latency change due to intraplantar inflammation…….......................................11 3.1.1.1 Saline 3.1.1.2 CFA 3.1.1.3 Carrageenan 3.1.2 Increased responses to mechanical stimuli due to intraplantar inflammation………………………………......13 3.1.2.1 Saline 3.1.2.2 CFA 3.1.2.3 Carrageenan 3.1.3 Nociceptive sensitivity change due to intramuscular inflammation…...........................14 3.1.3.1 Radiant heat test 3.1.3.2 Von Frey filament test 3.2 Pathology examination………………………………………14 3.2.1 External appearance……………………………………..15 3.2.2 Histological examination of the paw……………....15 3.2.3 Histological examination of the muscle…………...16 3.2.3.1 Saline 3.2.3.2 CFA 3.2.3.3 Carrageenan 3.3 Determination of gene expression level in dorsal root ganglia………………....................................18 Chapter 4: Discussion…………………………………………..20 4.1 Behavioral response differences in different inflammation models…………............................20 4.1.1 ASIC3 knockout mice exhibited no mechanical hyperalgesia and attenuated thermal hyperalgesia after cutaneous insult………..……...........................20 4.1.2 Muscle inflammation had no effect on thermal sensitivity……………..................................21 4.2 Pathology characterization of inflammation under different models…………...............................22 4.2.1 Granuloma formation is altered in ASIC3 knockout mice…………….........................................23 4.2.2 ASIC3 knockout mice were less susceptible to vasculitis……………...................................25 4.2.3 ASIC3 and neurogenic inflammation………………………………….................26 4.2.4 Correlations between pathological features and behavior responses…...................................27 4.2.5 Inflammation, the two-edged sword……………………27 4.3 Gene expression level change in response to inflammation………………….............................28 4.3.1 Uncoordinated information reguarding to inflammation-mediated ion channel up-regulation in different studies..29 4.3.2 Nav1.9 and its role in inflammatory pain response relating to ASIC3......................................30 Chapter 5: Conclusion…………………………………………..31 Reference…………………………………………………………..32 Appendix: List of primers……………………………………..56 | |
dc.language.iso | en | |
dc.title | 第三型酸敏性離子通道調節發炎引起的疼痛過敏化現象 | zh_TW |
dc.title | The Role of ASIC3 in Inflammation Mediated Hyperalgesia | en |
dc.type | Thesis | |
dc.date.schoolyear | 95-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 閔明源(Ming-Yuan Min) | |
dc.contributor.oralexamcommittee | 孫維欣,黃翊恭 | |
dc.subject.keyword | 第三型酸敏性離子通道,發炎,疼痛過敏化,肉芽腫,血管炎,基因表現, | zh_TW |
dc.subject.keyword | ASIC3,hyperalgesia,inflammation,neurogenic inflammation,Nav1.9,granuloma,vasculitis,gene expression, | en |
dc.relation.page | 36 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2007-07-30 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 動物學研究研究所 | zh_TW |
顯示於系所單位: | 動物學研究所 |
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