臺灣博碩士論文加值系統

中文摘要
使用注射式麻醉方法於實驗用小型嚙齒動物，包括黃金倉鼠可便於進行各種實驗和外科手術之進行。Medetomidine（MED）是一種親脂性α2型腎上腺素性受體刺激劑，具有鎮靜、止痛、解除焦慮和肌肉鬆弛作用。它可與解離性麻醉劑ketamine（KET）合用，且能增強KET的麻醉和肌肉鬆弛作用。MED的藥物作用可被其特異性拮抗劑—atipamezole（AMZ）所翻轉，使動物快速甦醒和回復正常生理狀態。本研究之目的在尋求適合於黃金倉鼠的MED-KET外科麻醉組合劑量，同時評估6種AMZ不同劑量對MED-KET麻醉之拮抗效果。本實驗係由腹腔內注射7種不同之MED-KET（0.125-125、0.25-100、0.25-125、0.25-150、0.5-100、0.5-125和0.5-150 mg/kg）組合劑量，以觀察對性成熟之雌性和雄性黃金倉鼠之麻醉作用和藥物作用時間是否具有性別差異性。藥物注射後記錄動物出現共濟失調時間、失去翻正反射時間、全身不動時間、反射回復時間（眼瞼、角膜、前趾和後趾反射）、身體各部分自行活動時間（頭部、前肢和後肢）、回復翻正和自行爬行時間。利用疼痛刺激的反應、趾反射和肌肉鬆弛度等判定麻醉深度，並計算制動時間（身體完全不動期間）、甦醒時間、睡眠時間（失去翻正反射期間）和外科麻醉期（後趾反射消失期間）。結果顯示實驗鼠對各項測試反應時間可隨劑量增高而明顯增加。所有劑量組皆可在麻醉恢復時觀察到多尿現象。雖然所有動物皆失去痛覺反應，但以0.5-125 mg/kg劑量組最能產生一致之外科麻醉期（雄鼠：平均69.9 ± 5.4分鐘；雌鼠：平均54.0 ± 2.9分鐘）。在性別差異方面，於MED-KET同劑量組之雄鼠各種測試反應時間可較雌性者為長。MED-KET（0.25-125 mg/kg、0.25-150 mg/kg和0.5-150 mg/kg）引起之雄鼠外科麻醉期亦較雌鼠為長。使用6種（0.0625-2 mg/kg）AMZ劑量係於MED-KET（0.5-125 mg/kg）麻醉30分鐘後由腹腔內給藥，對照組則給予等容積之0.9％食鹽水（1 ml/200 mg 體重）。結果顯示與對照組比較，各劑量均能翻轉MED-KET引起之麻醉作用。0.25、0.5、1和2 mg/kg AMZ劑量組間無明顯差異（P＞0.05）。0.0625 mg/kg AMZ與0.125 mg/kg AMZ對MED-KET引起之甦醒時間、睡眠時間和制動時間具有顯著差異，0.0625 mg/kg組皆較0.125 mg/kg組者為長。在性別差異方面，於AMZ同劑量組之雄鼠的回復翻正時間、自行爬行時間、制動時間和睡眠時間可較雌性者為長。由本研究結果顯示MED-KET（0.5-125 mg/kg）合劑使用於黃金倉鼠可產生40分鐘以上之外科麻醉期，AMZ回轉麻醉之最佳劑量為0.125 mg/kg。

Summary
Injection anesthesia is a common practice useful for laboratory small rodents such as golden hamsters in various experiments and surgical procedures. Medetomidine (MED) is a lipophilic α2-adrenoreceptor agonist with good sedative, analgesic, anxielytic and muscle relaxation effects. MED, when combined with ketamine (KET) can enhance the anesthetic effect and muscle relaxation produced by KET. Atipamezole (AMZ), an α2-adrenoreceptor antagonist, can reverse the effects of MED and reduce the recovery time. The aims of this study were to find out the suitable combinational dosage of MED-KET for golden hamsters in surgical anesthesia and to evaluate the antagonistic effects of AMZ at six dosages to MED-KET-induced anesthesia. Sex-matured male and female golden hamsters were administered with combinations of MED-KET (0.125-125, 0.25-100, 0.25-125, 0.25-150, 0.5-100, 0.5-125 and 0.5-150 mg/kg) intraperitoneally and evaluated for their anesthetic efficacy. Parameters that were recorded after the drug administration include time to ataxia, time to loss of righting reflexes, time to loss of purposeful movements, time to response to stimulation (corneal, palpebral, front and rear legs), and time to recovery of righting reflex and crawl. The depth of anesthesia was evaluated by aversive stimuli, pedal withdrawal reflex, muscle relaxation, immobilization (the period of no movements), arousal time, sleep time (the period of losing the righting reflex), and surgical anesthesia (the period of losing the rear pedal withdrawal reflex). The data indicated that most of the MED-KET combinations produced dose-dependent anesthetic effects in golden hamsters. Polyuria was observed in all MED-KET combinations. While all MED-KET combinations were capable of eliminating pain perception in hamsters, the MED 0.5 mg/kg-KET 125 mg/kg produced the most steady surgical anesthesia (averaged surgical anesthesia time: male: 69.9 ± 5.9 min, female: 54.0 ± 2.9 min). Male hamsters tended to need a longer response time than female hamsters in most parameters, which was indicated by a significant longer steady surgical anesthesia in the following MED-KET (0.25-125 mg/kg, 0.25-150 mg/kg, and 0.5-150 mg/kg) combinations. To evaluate for the antagonistic effect of AMZ, six different AMZ (0.0625-2 mg/kg) dosages or 0.9 % saline (1 ml/200 mg BW) were given to hamsters 30 minutes following MED-KET (0.5-125 mg/kg) injection. The results indicated that all six AMZ dosages were effective in reversing the anesthetic effects of MED-KET; however, there was no significant differences among 0.25, 0.5, 1, and 2 mg/kg AMZ groups (P > 0.05). The 0.0625 mg/kg AMZ group exhibited significantly longer arousal time, sleep time, and immobilization time than the 0.125 mg/kg group. In the same AMZ dose, male hamsters had longer sleep time, immobilization time, righting reflex time, and time to spontaneous crawl. Results of this study indicated that MED-KET (0.5-125 mg/kg) could induce at least 40 mins of steady surgical anesthesia, the best dosage for AMZ to effectively reverse this MED-KET-induced anesthesia in golden hamsters was 0.125 mg/kg.

目錄
中文摘要………………………………………………………………………...…….....i
英文摘要……………………...……………………………………………………….. iii
目錄………………………………….……………….……………………………….…v
表次........…………..……………………………….…………………………...…..…viii
圖次........…………………….………………………………………………………......x
第一章　緒言…………………………………………………....………………….…. 1
第二章　文獻探討……………………………………………… ……………………..7
第一節 Medetomidine…………………………………..…………..………………... 7
一、α2型腎上腺素性受體刺激劑簡介...……………………………………………... 7
二、Medetomidine對於α2型腎上腺素性受體之選擇性和專一性…………………12
三、作用機制...………………………………………………………………….……. 13
四、藥理作用…………………………………………………………………………. 13
五、人類醫學之研究…………………………………………………………………..21
六、獸醫學之應用…………………………………………………………………….. 22
（一）Medetomidine……………………………………………………………………22
（二）Medetomidine與ketamine併用………………….……………..…………….. 22
（三）Medetomidine與propofol併用…………………..…………………….……... 25
（四）Medetomidine與類鴉片藥物併用………………..…………………………… 25
第二節 Ketamine………………………………………………..……………………26
一、簡介………………………………………….………………………….…………26
二、作用機制…………………………………….……………………….……………27
三、藥理作用…………………………………….………………..……………………27
四、人類醫學之應用…………………...……………………………………...……….27
五、獸醫學之應用……………………...………………………………………………28
第三節　Atipamezole……………………………….………………….…………..… 29
一、α2型腎上腺素性受體拮抗劑簡介……………………………….……………… 29
二、Atipamezole對於α2型腎上腺素性受體之選擇性和專一性……………..……. 30
三、作用機制…………………………………………….………………………..……30
四、藥理作用…………………………………………….………………….....……….30
五、人類醫學之應用…………………………………….…………………….…...…..31
六、獸醫學之應用……………………………………………………………………. 32
第四節　麻醉判定探討…………………………………………………………...…. 36
一、導入麻醉期………………………………………………………………….….... 37
二、保護性反射………………………………………………………………………. 37
三、對疼痛刺激的反應…………………………………………………………….. …40
四、肌肉鬆弛度…………………………………………………….……………….. ..41
五、麻醉回復期…………………………………………………….………………….42
六、麻醉深度……………………………………………………….….……………... 42
七、翻轉麻醉…………………………………………………………………………. 46
第五節　注射方式探討………………………………………………….…………. ..47
第三章　材料與方法............…………………………………………………..……. .50
一、實驗動物…………………………………..…………………………..………….. 50
二、飼養管理………………………………………………………………………….. 50
三、麻醉合劑的配製………………………………………….. ………………………50
四、麻醉合劑的注射方式………………………..…………………………………… 51
五、預備實驗………………………………………………………………………...…52
六、正式實驗………………………………………………….........………………….52
七、統計分析…………………………………………………………………………...58
第四章　結果…………………………………………….……………………………59
第五章　討論………………………………………………………………….………84
參考文獻…………………………………….…………………………………….…...92

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