指導教授:張芳嘉臺灣大學:獸醫學研究所方淳瀅FANG, CHUN-YINGCHUN-YINGFANG2014-12-012018-07-092014-12-012018-07-092013http://ntur.lib.ntu.edu.tw//handle/246246/264497失眠是最普遍的睡眠疾患之一。中草藥天麻在中國傳統醫學被用於抑制痙攣和失眠的治療。本研究探討天麻萃取物 T1-11在正常大鼠及失眠大鼠中,是否能發揮促進睡眠的作用,並進一步評估腺嘌呤1型受器與腺嘌呤2A型受器,是否參與 T1-11 之促眠作用。本研究結果發現,在正常大鼠施打 T1-11 會增加非速眼動睡眠,但對速眼動睡眠量則沒有顯著影響。T1-11 造成之非速眼動睡眠量增加,不會被選擇性腺嘌呤1型受器拮抗劑DPCPX阻斷,但會被選擇性腺嘌呤2A型受器拮抗劑 SCH 58261 阻斷,暗示腺嘌呤2A型受器在T1-11之促眠作用中所扮演的角色。T1-11亦會增加失眠大鼠之非速眼動睡眠,為T1-11將來應用於臨床失眠治療的可能性,提供支持性證據。The rhizomes of Gastrodia elata, have traditionally been used in Chinese medicine for seizure suppression and the treatment of insomnia. This study was performed to investigate whether T1-11, an ethanol extract (an active ingrediant) of G. elata, produces somnogenic effects in normal and insomniac rats. We further evaluated the involvement of adenosine 2A receptors (A2AR) and adenosine 1 receptors (A1R) in the T1-11-mediated somnogenic effects. Administration of T1-11 increased non-rapid eye movement (NREM) sleep. The amount of rapid-eye movement (REM) sleep was not significantly changed. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A1R antagonist, did not block the T1-11-induced enhancement of NREM sleep, whereas 5-amino-7-(β-phenylethyl)-2-(8-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH 58261), a selective A2AR antagonist, significantly blocked the T1-11-induced enhancement of NREM sleep, indicating the role of A2AR in the somnogenic effect of T1-11. T1-11 increased NREM in the insomniac rats, providing evidence for the potential use of T1-11 in the treatment insomnia in clinic.TABLE OF CONTENTS ABSTRACT 1 INTRODUCTION 3 MATERIALS AND METHODS 11 2.1 Drugs 11 2.2 Animals and surgeries 12 2.3 Apparatus 13 2.4 Experimental protocols 15 2.4.1 To determine the effect on spontaneous sleep 15 2.4.2 Cage-exchange-induced insomnia 16 2.5 Statistical analysis 16 RESULTS 18 3.1 Effects of intracerebroventricular administration of CGS 21680 in rats 18 3.2 Effects of intracerebroventricular administration of T1-11 in rats 19 3.3 Role of adenosine receptors in the somnogenic effect of T1-11 in rats 21 3.3.1 Effect of the selective adenosine 1 receptor antagonist (DPCPX) on the T1-11-induced enhancement of NREM sleep 21 3.3.2 Effect of the selective adenosine 2A receptor antagonist (SCH 58261) on the T1-11-induced enhancement of NREM sleep 23 3.4 Insomniac rats: cage exchange model 24 3.5 The somnogenic effect of T1-11 in insomniac rats 25 DISCUSSION 27 4.1 The somnogenic effect of T1-11 in normal rats 27 4.1.1 T1-11 enhanced NREM sleep in a two-phase manner 29 4.1.2 T1-11 exhibited a bell-shape dose-dependent curve 30 4.1.3 SCH 58261, but not DPCPX, blocked the T1-11 – induced NREM sleep enhancement 33 4.2 The somnogenic effects of T1-11 in insomniac rats 35 4.2.1 The cage-exchange insomnia model 35 4.2.2 The somnogenic effect of T1-11 in insomniac rats 38 FIGURES 43 TABLES 63 REFERENCES 692520587 bytesapplication/pdf論文公開時間:2018/11/05論文使用權限:同意有償授權(權利金給回饋本人)T1-11天麻腺嘌呤受器失眠大鼠天麻萃取物 T1-11 於大鼠之促眠作用The somnogenic effects of T1-11, derived from Gastrodia elata, in Ratsthesishttp://ntur.lib.ntu.edu.tw/bitstream/246246/264497/1/ntu-102-R99629037-1.pdf