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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 呂俊宏(June-Horng Lue) | |
dc.contributor.author | Yen-Wei Lin | en |
dc.contributor.author | 林彥維 | zh_TW |
dc.date.accessioned | 2021-06-15T12:44:39Z | - |
dc.date.available | 2021-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-07-26 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50527 | - |
dc.description.abstract | MMPs 是種以鋅離子作為輔因子的胜肽內切酶,可以降解細胞外基質;在正常狀況,這類蛋白酶與傷口癒合及修復有關,而近年來研究發現周邊神經損傷時,它們與神經病變疼痛有所關聯,研究著重於 MMP-9在後肢坐骨神經損傷模式中扮演的角色,缺乏探討 MMP-9在上肢神經病變疼痛中參與機制的相關研究。故本研究以正中神經慢性纏繞傷害的動物模式模擬腕隧道症候群,分析探討MMP-9 在正中神經病變疼痛中如何因應及其可能的功能。
在一般正常情況下,MMP-9在正中神經及頸髓段背根神經節神經元中免疫化學反應程度相當微弱稀少,但正中神經慢性纏繞傷害後一天,其免疫化學反應程度有顯著的上升,延至傷害後一週仍然有顯著高於正常的神經及背根神經節。在纏繞損傷一天的正中神經不僅MMP-9免疫化學反應增加,且TNF-α及IL-1β也有明顯增強,但MBP卻有明顯地減少。另外在神經傷害後一週的背根神經節神經元中,MMP-9 與 galanin 、 nNOS 及NPY 雙重標誌神經元佔背根神經節的比例都有顯著增加。若在正中神經慢性纏繞傷害手術當下給與 MMPs 抑制劑 (GM6001) 處理,結果發現損傷的正中神經與背根神經節神經元中MMP-9免疫化學反應程度都有明顯下降,而前述雙重免疫標誌的比率都有明顯減緩,唯獨正中神經中MBP有顯著回升。接著在疼痛行為測試中,發現正中神經慢性纏繞傷害後,實驗動物有呈現觸覺痛及熱痛覺過敏行為表現;然而神經慢性纏繞傷害當下即給予GM6001,其神經病變疼痛行為則獲得改善,同時電刺激所引發楔狀神經核中 c-Fos 神經元數量亦有顯著的下降;但是在神經傷害後三天後才給予GM6001,實驗動物神經病變疼痛行為改善程度卻不顯著,其楔狀神經核中 c-Fos 神經元數量亦與載體控制組相似。 綜合以上研究結果,推論MMP-9 在正中神經慢性纏繞傷害可能受到TNF-α或IL-1β誘導增加而分解MBP造成去髓鞘作用,進而誘發背根神經節神經元galanin、nNOS 及NPY等增加而影響神經病變疼痛的產生。 | zh_TW |
dc.description.abstract | MMP is a family of endopeptidase using Zn2+ as a co-factor degrades extra cellular matrix. In general, this kind of proteinase is involved in wound healing and recovery. Recently, studies have reported that MMPs play an important roles in neuropathic pain while the peripheral nervous system is injured. However, most of these studies focused on the role of MMP-9 in the sciatic injury model. There is nearly no study about the MMP-9-related pathway in the upper limb neuropathic pain. Thus, in our study, a median nerve chronic constriction injury model is set to simulate the carpel tunnel syndrome and investigate the mechanisms of MMP-9 in the median nerve neuropathic pain.
Normally, the level of MMP9 immunoreactivity in the median nerve and cervical dorsal root ganglion (DRG) are rarely observed. However, one day after chronic constriction injury, the level of MMP9 immunoreactivity obviously increased. After one week, the level of MMP9 immunoreactivity is still significantly increased in the injured median nerve and DRGs. Besides the higher level of MMP9 immunoreactivity, the amounts of TNF-α and IL-1β immunoreactivity also obviously increased, the level of MBP immunoreactivity, and vice versa. Similarly, one week after nerve injury, the neurons with double labeling of MMP9 with galanin, nNOS, or NPY are significantly increased in the DRG. However, with the treatment of MMPs inhibitor (GM6001) in the median nerve injury surgery, the level of MMP immunoreactivity in the median nerve and DRG neurons are decreased. In addition, the rations of the above-mentioned double labeling DRG neurons also significantly decreased. Only the level of MBP immunoreactivity in the median nerve is significantly increased. In the pain behavioral test,the median nerve CCI rats displayed allodynia and hyperalgesia. But, CCI rats the neuropathic pain behaviors were alleviated by GM6001 treatment. Furthermore, following electrical stimulation injured median nerve-caused, the number of c-Fos neurons in the cuneate nucleus is significantly decreased by GM6001 treatment. In conclusion, these results suggested that the level of MMP9 is increased due to the stimulation of TNF-α or IL-1β, thus decomposing the MBP and causing the demyelination. This might result in higher levels of galanin, nNOS, and NPY, causing the neuropathic pain. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T12:44:39Z (GMT). No. of bitstreams: 1 ntu-105-R03446009-1.pdf: 3795756 bytes, checksum: 4eab7d3cc4dfd91740cf2109613f97d5 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 口試委員會審定書 iii
致謝 iv 中文摘要 v Abstract vii 壹、緒論 1 一、神經病變疼痛 (neuropathic pain) 1 二、MMP-9與神經損傷的關係 2 三、其他痛覺相關因子 4 四、背柱-內側蹄系路徑與神經病變疼痛之關係 10 五、原始致癌基因 (Proto-oncogene) c-fos 11 六、實驗目的 12 貳、實驗材料與方法 13 一、實驗動物 13 二、正中神經慢性纏繞傷害動物模式與藥物處理 13 三、前肢掌內藥物注射之動物行為測試 13 四、藥物處理與電刺激 15 五、灌流犧牲 15 六、組織製備 16 七、免疫組織化學染色 (Immunohistochemistry, IHC) 17 八、正中神經與背根神經節中不同品系抗體之雙重免疫螢光標誌 19 九、影像分析與定量 21 参、結果 22 一 、MMP-9於正中神經中之表現情形 22 二、MMP-9 與 疼痛相關因子於正中神經中雙重螢光標誌情形 22 三、MMP-9免疫反應神經元於第六頸髓段背根神經節中的數量變化 23 四、MMP-9 與疼痛相關因子於第六頸髓段背根神經節中之雙重螢光 24 五、以不同方式給予 MMPs 抑制劑 (GM6001) 探討 MMP-9對正中神經慢性纏繞傷害所引發之神經病變疼痛影響 27 六、 c-Fos 免疫陽性神經元於受傷側正中神經電刺激後之表現情形 29 肆、討論 30 一、 正中神經慢性纏繞傷害後 MMP-9 在正中神經與背根神經節中的免疫標誌變化 30 二、 MMP-9 於周邊神經損傷後與其他疼痛相關因子間的關係 31 三、 MMP-9 在神經變病疼痛中的角色 34 伍、參考文獻 36 陸、圖與圖說 46 | |
dc.language.iso | zh-TW | |
dc.title | MMP-9 在正中神經病變疼痛中所扮演的角色 | zh_TW |
dc.title | The Role of MMP-9 in the Median Nerve Neuropathic Pain | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 溫振源(Chen-Yuan Wen),蔡怡汝(Yi-Ju Tsai),陳淑華(Seu-Hwa Chen),林至德(Chi-Te Lin) | |
dc.subject.keyword | 正中神經,神經病變疼痛,楔狀神經核,背根神經節, | zh_TW |
dc.subject.keyword | MMP-9,median nerve,neuropathic pain,cuneate nucleus,DRG, | en |
dc.relation.page | 80 | |
dc.identifier.doi | 10.6342/NTU201601374 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-07-26 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 解剖學暨細胞生物學研究所 | zh_TW |
顯示於系所單位: | 解剖學暨細胞生物學科所 |
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