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研究生:邱俊賢
研究生(外文):Chun-Hsien Chiu
論文名稱:探討大鼠之多巴胺D2型接受器調控脊髓反射增益現象
論文名稱(外文):Dopaminergic D2 receptor Modulates the Spinal Reflex Potentiation in Rats
指導教授:董光中董光中引用關係
指導教授(外文):Kwong-Chung Tung
學位類別:碩士
校院名稱:國立中興大學
系所名稱:獸醫學系暨研究所
學門:獸醫學門
學類:獸醫學類
論文種類:學術論文
畢業學年度:97
語文別:中文
論文頁數:50
中文關鍵詞:多巴胺脊髓反射增益現象NMDAAMPA
外文關鍵詞:dopaminespinal reflex potentiationNMDAAMPA
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多巴胺神經系可經由 D2 接受器(D2R)抑制蛋白質激酶 A(PKA),使之在脊髓上產生抑制作用。近年來,我們實驗室提出一種新型態且與疼痛相關的神經可塑性–脊髓反射增益現象(SRP),且推測可經由 PKA 依賴性的路徑使之產生發炎後的敏感作用。然而,多巴胺神經系在 SRP 上的調控作用還未被探討。因此在本實驗中,我們嘗試去決定多巴胺神經系在 SRP 上所扮演的角色,以及在活體上多巴胺可能參與的細胞內傳訊機制。椎管內投予 D2R 致效劑,紀錄與分析給藥前後,重複性電刺激(RS,1 stimulation/sec)外尿道括约肌動作電位(EUSE)之活性。我們發現椎管內投予 D2R 致效劑 Q110 後(RS + Q),會減弱 RS 引發的 SRP,且前投予 D2R 拮抗劑 L135(RS + L + Q)可以逆轉此抑制作用。而且麩氨酸類接受器的致效劑 NMDA 與 AMPA,都可以拮抗 D2R 致效劑在 SRP 上所產生的抑制作用。有趣的是與 AMPA 致效劑相較之下,NMDA 致效劑對於 D2R 致效劑所造成的抑制作用,有更高的拮抗性。此外,PKA 的活化劑 forskolin,亦可逆轉 D2R 致效劑在 SRP 上所造成的抑制作用。綜合以上結果,我們推測多巴胺神經系在脊髓上可能會經由 D2R 去調控 SRP,此可作為往後臨床上病理狀態下痛覺傳導之參考。
Dopaminergic innervations on the spinal cord exhibit their inhibitory effect through the D2-like dopaminergic receptors (D2R)-dependent inhibition on protein kinase A (PKA). Recently, our laboratory reported a novel form of pain-related neural plasticity, the spinal reflex potentiation (SRP), which is presumed to underlie post-inflammatory hyperalgesia via PKA-dependent pathways. However, the effects of dopaminergic innervations on the SRP modulation have yet been established. In this study, we tried to determine the role of dopaminergic innervations in SRP and possible intracellular cascade involved using in vivo animal preparations. We recorded and analyzed the external urethra sphincter electromyography (EUSE) activity in response to repetitive stimulation (RS, 1 stimulation/sec) before and after intrathecal application of D2 agonist. We found that the intrathecal dopamine D2 agonist, Q110 (RS + Q), attenuated the RS-induced SRP that was reversed by pretreatment of L135, a dopamine D2 antagonist (RS + L + Q). Moreover, the glutamatergic receptor agonist, NMDA and AMPA agonist both antagonized the D2 agonist-elicited inhibition on SRP. Interestingly, when compared with AMPA agonist, NMDA exhibited a higher antagonistic effect of D2 agonist-elicited inhibition. In addiction, a PKA activator, forskolin, reversed D2 agonist-elicited inhibition on SRP. Together, these results suggest that dopaminerric innervations on the spinal cord might play roles in the modulation of SRP via D2R that is a possible target for the development of pharmacological strategies in the treatment of neuropathic pain.
中文摘要------------------------------------------------- i
英文摘要------------------------------------------------ ii
目次----------------------------------------------------iii
圖次-----------------------------------------------------iv
第一章、 緒言---------------------------------------------1
第二章、文獻探討------------------------------------------2
一、 神經支配與膀胱功能--------------------------------2
二、 多巴胺與麩氨酸在泌尿功能之作用--------------------3
三、 麩氨酸與神經傳導作用------------------------------5
四、 NMDA接受器的次單位組成與功能的特性----------------6
五、 NMDA與痛覺傳導------------------------------------7
六、 脊髓反射增益現象----------------------------------8
第三章、方法與材料---------------------------------------10
一、 實驗流程概述-------------------------------------10
二、 動物麻醉-----------------------------------------10
三、 外科手術-----------------------------------------11
四、 電刺激模式---------------------------------------13
五、 椎管內給予藥物-----------------------------------14
六、 實驗分析與統計-----------------------------------15
第四章、結果---------------------------------------------16
一、 反覆性電刺激引發骨盆-尿道反射塑性之增益現象------16
二、多巴胺 D2 型接受器之致效劑在骨盆-尿道反射塑性產生一
劑量-依賴性---------------------------------------16
三、 多巴胺 D2 型接受器在骨盆-尿道反射塑性之相關性----17
四、 多巴胺 D2 型接受器與 NMDA 及 AMPA 之關係性-------18
五、 多巴胺 D2 型接受器透過 PKA 調控 NMDA 與 AMPA-----18
第五章、討論---------------------------------------------32
參考文獻-------------------------------------------------37
附錄-----------------------------------------------------43
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