血清素受體2A和2B分別參與調控由完全弗氏劑或血清素所引發的熱痛覺敏感和機械性痛覺敏感

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邱永毅(Yuan-yi Chiu) 查詢紙本館藏

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生命科學系

論文名稱

血清素受體2A和2B分別參與調控由完全弗氏劑或血清素所引發的熱痛覺敏感和機械性痛覺敏感
(The roles of 5-HT2A and 5-HT2B in CFA- or 5-HT-induced thermal and mechanical hyperalgesia)

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摘要(中)

當我們受傷時，身體的周邊組織會釋放出發炎調節因子使得傷害性接受器被活化和敏感，造成發炎性疼痛的產生。血清素是一種重要的發炎調節因子，會被周邊組織的血小板和肥大細胞所釋放出來，參與在疼痛以及痛覺敏感現象。先前研究發現血清素受體2B/2C抑制劑，會抑制由血清素所引發的機械性痛覺敏感現象，但並不能抑制熱痛覺敏感現象。然而，目前依然不清楚是透過何種訊號傳遞路徑來調控血清素引發的機械性痛覺敏感現象，以及哪一個血清素受體調控熱痛覺敏感現象。在我的實驗結果發現，血清素受體2B是透過磷脂?Cβ-蛋白質激?Cε路徑，調控血清素引發的機械性痛覺敏感現象，並且辣椒素受體1也參與在其中調控。血清素受體2B參與完全弗氏佐劑所引發的機械性痛覺敏感現象前期。血清素所引發的熱痛覺敏感現象，是由血清素受體2A透過磷脂?Cβ-蛋白質激?Cε路徑所調控的。

摘要(英)

Following tissue damage, peripheral tissues release inflammatory mediators that activate and sensitize the nociceptors, inducing inflammatory pain. Serotonin (5-HT), one of the important inflammatory mediators, is released from platelets and mast cells and involved in pain and hyperalgesia. Previous studies have found that 5-HT2B/2C antagonist inhibits 5-HT-induced mechanical but not thermal hyperalgesia. However, it remains unclear which signaling pathways are involved in 5-HT-induced mechanical hyperalgesia and which 5-HT receptor mediates thermal hyperalgesia. I have found that 5-HT2B mediated 5-HT-induced mechanical hyperalgesia through phospholipase Cβ (PLCβ)-protein kinase Cε (PKCε) pathway. It was likely due to regulation of TRPV1. 5-HT2B is involved in CFA-induced mechanical hyperalgesia in the early phase. 5-HT-induced thermal hyperalgesia was mediated by 5-HT2A-Gq-PKCε pathway.

關鍵字(中)

★ 血清素
★ 血清素受體2A
★ 血清素受體2B
★ 機械性痛覺敏感
★ 熱痛覺敏感

關鍵字(英)

★ 5-HT
★ 5-HT2A
★ 5-HT2B
★ mechanical hyperalgesia
★ thermal hyperalgesia

論文目次

中文摘要 i
Abstract ii
目錄 iv
圖目錄 vi
第一章緒論 1
1.1痛覺 (Pain) 2
1.2痛覺訊息傳遞的過程 (Nociception) 2
1.3 發炎性疼痛 (Inflammatory pain) 3
1.4血清素引發的痛覺過敏 4
1.5血清素受體的分類與途徑 5
1.6與痛覺敏感相關的血清素受體 6
1.6.1 血清素受體1A (5-HT1A) 6
1.6.2 血清素受體2A (5-HT2A) 6
1.6.3 血清素受體2B (5-HT2B) 7
1.6.4 血清素受體3A (5-HT3A) 7
1.6.5 血清素受體4 (5-HT4) 8
1.6.6 血清素受體7 (5-HT7) 8
1.7 與痛覺敏感相關的離子通道 8
1.7.1 辣椒素受體1 (Transient receptor potential vanilloid channel 1, TRPV1) 8
1.8研究動機與目的 9
第二章材料與方法 11
2.1實驗材料 12
2.1.1 細胞株、菌株 12
2.1.2 實驗用動物 12
2.1.3 藥品 12
2.2實驗方法 13
2.2.1 勝任細胞的製備 13
2.2.2 大腸桿菌轉型作用 (Transformation)： 13
2.2.3 細菌培養 14
2.2.3.1菌液培養： 14
2.2.3.2 菌種保存： 14
2.2.4質體DNA製備 14
2.2.4.1質體小量製備 (Mini-prep)： 14
2.2.4.2 質體大量製備 (Midi-prep)： 15
2.2.4.3　Agarose gel的製備及電泳質體DNA檢測： 16
2.2.5痛覺行為實驗 16
2.2.5.1 機械性痛覺行為實驗 (Touch test) 16
2.2.5.2 熱痛覺行為實驗 (Plantar test) 17
2.2.6 繼代細胞培養 (Subculture) 17
2.2.7 轉染試驗 (Transfection) 18
2.2.8 鈣離子分析 (Single cell calcium imaging) 18
2.2.8.1人類胚胎腎臟細胞前處理 18
2.2.8.2鈣離子分析 19
2.2.9 統計分析 (Statistics) 19
第三章結果 20
3.1血清素受體2B或2B/2C的抑制劑可抑制血清素受體2B引發的胞內鈣離子增加 21
3.2 血清素引發的機械性痛覺敏感可以由血清素受體2B以及Gq protein路徑下游磷脂?Cβ和蛋白質激?Cε 抑制劑給抑制 22
3.3 抑制辣椒素受體1可以抑制辣椒素或血清素引發的機械性痛覺敏感現象 24
3.4血清素受體2A抑制劑可以抑制血清素受體2A引發的胞內鈣離子增加 25
3.5血清素引發的熱痛覺敏感現象可以由血清素受體2A以及Gq protein路徑下游磷脂?Cβ和蛋白質激?Cε 抑制劑給抑制 25
3.6血清素受體1A與血清素受體3A抑制劑可以分別抑制血清素受體1A與血清素受體3A引發的胞內鈣離子增加 27
3.7 血清素引發的熱痛覺敏感現象，不能被血清素受體1A或血清素受體3A選擇性的抑制劑給抑制 27
3.8 抑制辣椒素受體1可抑制辣椒素或血清素引發的熱痛覺敏感現象 28
3.9 血清素受體2B參與完全弗氏佐劑引發的機械性痛覺敏感現象 (前期)，血清素受體2A參與在完全弗氏佐劑引的熱痛覺敏感現象 29
第四章討論 31
4.1血清素受體2B會經由磷脂?Cβ和蛋白質激?Cε路徑，以及透過辣椒素受體1，參與調控血清素所引發的機械性痛覺敏感 32
4.2 血清素引發的熱痛覺敏感現象，是由血清素受體2A參與調控並且經由磷脂?Cβ和蛋白質激?Cε路徑 33
第五章文獻參考 38

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指導教授

孫維欣(Wei-Hsin Sun)

審核日期

2014-6-26

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