臺灣博碩士論文加值系統

奧迪氏括約肌 (Sphincter of Oddi) 在調控膽汁、胰液分泌至十二指腸扮演很重要之角色，當其功能失常時臨床上常見右上腹部脹痛、腸脹氣、黃疸、嘔吐及消化不良等，如西方醫學之膽石症、手術後奧迪氏括約肌功能不全、慢性胰臟炎、肝後性鬱積型肝炎、阻塞性黃膽，在中醫典籍對其病症常以脅痛、肝脹、膽脹及結胸等來描述。
本研究主要分為有二部分；partⅠ：探討電針 (Electroacupuncture)麻醉後貓的右側期門、日月穴20分鐘後取出膽囊、奧迪氏括約肌及十二指腸，經免疫染色法來探討其細胞組織形態之變化，進而了解CCK內分泌細胞、VIP神經分佈狀況。partⅡ：以濃縮中藥木香檳榔丸經鼻胃管灌食麻醉後之兔子來探討其奧迪氏括約肌1小時中之壓力變化及調控機轉。
實驗結果發現電針麻醉後貓的右側期門、日月穴20分鐘後膽囊、奧迪氏括約肌及十二指腸之CCK (Cholecystokinin)分泌細胞及VIP (Vasosctive intestinal polypetide)神經數量，經免疫染色後以半定量評分計量評估後發現比未電針前之CCK分泌細胞及VIP神經數量表現更多且明顯，證明了電針麻醉後貓的右側期門、日月穴可激發CCK分泌細胞及VIP神經的表現，進而調控奧迪氏括約肌。以不同劑量（0.25 gm、0.5 gm、1.0 gm、2.0 gm）的傳統中藥處方木香檳榔丸經由鼻胃管灌食麻醉後的兔子，來測量1小時中奧迪氏括約肌壓力之變化。在實驗中我們得到的結果是：不同劑量的木香檳榔丸對麻醉後之兔子在灌食後1小時內基礎壓 (tonic pressure)、相位收縮壓 (phasic contraction pressure)有不同程度之改變且有統計學上的意義。其作用機轉；一：可被先施予靜脈給藥之A.P.P. 所阻斷可證明其作用機轉非經由NANC (Nonadrenegic Noncholinergic) pathway 。二：可被事先施予鼻胃灌食之pirenzepine 10 mg/kg（為專一性的M1 Muscarinic receptors之拮抗劑）所阻斷。因此木香檳榔丸對奧迪氏括約肌之生理調控機轉可推測興奮了M1 Muscarine receptors而來。
所以，我們結論，傳統中國醫藥學在疾病治療中，電針及中藥方劑 (木香檳榔丸) ，對動物奧迪氏括約肌的調控機轉，各扮演不同之重要角色。

The sphincter of Oddi (SO) plays an important role in regulating the bile flow into the duodenum. According to Chinese literatures, many chest and abdomen acupoints and Chinese medicine drugs could treat acute abdomen diseases。Our previous studies demonstrated that electroacupunture (EA) modulated the SO motility in rabbits and cats through activation of non-adrenergic non-cholinergic (NANC) pathway。Now； We had designed two studies to investigate the changes of SO
Part I：This study designed to investigate the changes of neurotransmitters such as CCK and VIP in lower biliary tract in cats receiving EA stimulation. After cats were anesthetized with intramuscular injection of ketamine hydrochloride, they were prepared to conduct EA stimulation on right Qimen (LR14) and Riyue (GB24). The parameters of EA were 6 pulses/ 3 sec and 45 pulses/ 3sec alternatively in frequency, 1-2 mA in intensity and 20 min in stimulation duration. After the comptleteness of EA stimulation, visceral organs such as gallbladder, duodenum and the sphincter of Oddi were removed and frozen for immunohistochemistry localization of CCK and VIP. The results showed that the distribution of CCK-labelled cells in duodenum, gallbladder and SO were more and distinct after EA than before EA stimulation. Whereas, the VIP-labelled cells were significantly more and distinct in duodenum and SO, but not in gall bladder. We conclude that EA regulates the billiary motility though increasing the distribution of CCK- and VIP- containing cells in duodenum and the sphincter of Oddi.
Part II：This study was designed to investigate the effect of Chinese Medicinal Herbs MUH-SHIANG-BIN-LANG-WAN (MSBLW) and their mechanism of action on regulating the motility of SO in rabbits. The activity of SO in anesthetized rabbits was measured by using a continuously perfused open-tip manometric method. The rabbits were crammed with different doses of MSBLW through naso-gastric tubes. The SO motility before and after the administration of MSBLW were recorded, and analyzed with a computer equipped with an off line analysis software. The results showed that the SO activity, in terms of tonic pressure and phasic contraction pressure, were significantly changed with a dose-dependent manner. A significant lower tonic pressure and a higher phasic contraction pressure were noticed 40-60 min after administration of MSBLW with the peak response at 0.5-1.0 gm range. The responses were blocked by pretreatment of muscarinic receptors (M1) antagonist, pirenzepine (10mg/kg). We conclude that MSBLW is effective in increasing the SO motility through activation of M1 muscarinic receptors, which provides an evidence-based application of MSBLW in the treatment of biliary disorders.

目　錄
第一章　前言 1
第二章　文獻探討 2
第一節　奧迪氏括約肌 (Sphincter of Oddi) 之簡介 2
一、不同物種SO之解剖學比較 2
二、不同物種SO生理學的比較 2
三、SO功能之體內調節控制的物質 5
四、SO功能之體內調控的方式 8
五、SO之病理狀態 8
第二節　SO病理狀態之臨床舉例-膽石症 (cholelithiasis) 及中西醫觀點 10
一、西醫觀點 10
二、中醫觀點 11
第三節　現代治療膽石症 (cholelithiasis) 之挑戰 16
一、西醫的治療 16
二、中醫的治療 16
三、中西醫整合治療 16
第三章　材料與方法 17
PART Ⅰ 貓：組織免疫學染色篇 17
第一節　實驗動物 17
一、貓 17
第二節　實驗儀器、材料與設備 18
一、實驗儀器 18
二、材料 18
三、器械、設備 19
第三節　實驗方法 20
一、術前準備 20
二、電針模型的建立 20
三、免疫染色法（Immunohistochemistry stain.） 20
第四節　實驗設計及分組 23
一、探討電針對貓腸道組織免疫學之效應 23
二、探討假電針對貓腸道組織免疫學之效應 23
三、實驗對照組 23
第五節　染色正反應結果百分比計分評估表之設定 23
PART Ⅱ 兔子：濃縮中藥，木香檳榔丸篇 24
第一節　實驗動物 24
一、兔子 24
第二節　實驗儀器、材料與設備 24
一、實驗儀器 24
二、藥物材料 25
三、器械、設備 26
第三節 實驗方法 28
一、動物實驗模型建立 28
第四節　鼻胃管灌食藥物之模型的建立 34
一、胃大彎近幽門處解剖定位 (圖3-5) 34
第五節　實驗設計及分組 34
一、探討木香檳榔丸對兔子奧迪氏括應約肌之調控效應 34
二、探討木香檳榔丸對兔子奧迪氏括應約肌之作用機轉 36
第六節　實驗數據處理及統計方法 37
一、實驗數據處理 (圖3-6) 37
二、統計方法 37
第四章　結果 39
PART I 貓：組織免疫學染色篇 39
第一節　EA group (電針組) 對貓腸道組織免疫學之反應 39
第二節　Sham EA group (假電針組) 對貓腸道組織免疫學之反應 39
第三節　實驗對照組對貓腸道組織免疫學之反應 44
PARTⅡ　兔子：濃縮中藥--木香檳榔丸篇 45
第一節　木香檳榔丸濃縮中藥對兔子奧迪氏括約肌的效應 45
第二節　木香檳榔丸濃縮對兔子奧迪氏括約肌調控之作用機轉 58
第三節　木香檳榔丸濃縮對兔子奧迪氏括約肌調控之結論 71
第五章　討論 72
第一節　麻醉對奧迪氏括約肌之影響 72
第二節　奧迪氏括約肌的探討與實驗動物的選取 74
第三節　電針與手針參數的取捨 75
第四節　動物穴位之選擇 76
第五節　濃縮中藥之選擇 77
第六節　木香檳榔丸濃縮中藥之生藥基源與成品鑑定 78
第七節　木香檳榔丸調控奧迪式括約肌有效成份之預測 87
第八節　針刺、溫灸及中藥方劑木香檳榔丸之臨床適用性 88
第六章　結論 89
一、PART I 貓：組織免疫學染色篇 89
二、PART II 兔子：濃縮中藥木香檳榔丸篇 89
參考文獻 90
英文摘要 95
謝辭 97
圖目錄
【圖2.1】人類奧迪氏括約肌立體結構示意圖 3
【圖2.2】負鼠奧迪氏括約肌立體結構示意圖 4
【圖3.1】貓電針穴位之解剖定位 21
【圖3.2】貓腹部實景圖 22
【圖3.3】兔子鼻胃插管實景圖 29
【圖3.4】兔子腹部手術及插管實景圖 30
【圖3.5】兔子鼻胃插管，胃大彎近幽門處示意圖 35
【圖3.6】奧迪式氏括約肌壓力圖及實驗數據之定義 38
【圖4.1】貓膽囊免疫學染色圖 41
【圖4.2】貓奧迪氏括約肌免疫學染色圖 42
【圖4.3】貓十二指腸免疫學染色圖 43
【圖4.4】木香檳榔丸0.25gm (MSBLW) 對麻醉後兔子奧迪氏括約肌壓力圖之變化 46
【圖4.5】木香檳榔丸0.25gm (MSBLW) 對麻醉後兔子奧迪氏括約肌基礎壓力（TP）之變化統計圖 47
【圖4.6】木香檳榔丸0.25gm (MSBLW) 對麻醉後兔子奧迪氏括約肌相位收縮壓力（PP）之變化統計圖 48
【圖4.7】木香檳榔丸0.5gm (MSBLW) 對麻醉後兔子奧迪氏括約肌壓力圖之變化 49
【圖4.8】木香檳榔丸0.5gm (MSBLW) 對麻醉後兔子奧迪氏括約肌基礎壓力（TP）之變化統計圖 50
【圖4.9】木香檳榔丸0.5gm (MSBLW) 對麻醉後兔子奧迪氏括約肌相位收縮壓力（PP）之變化統計圖 51
【圖4.10】 木香檳榔丸1.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌壓力圖之變化 52
【圖4.11】 木香檳榔丸1.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌基礎壓力（TP）之變化統計圖 53
【圖4.12】 木香檳榔丸1.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌相位收縮壓力（PP）之變化統計圖 54
【圖4.13】 木香檳榔丸2.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌壓力圖之變化 55
【圖4.14】 木香檳榔丸2.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌基礎壓力（TP）之變化統計圖 56
【圖4.15】 木香檳榔丸2.0 gm (MSBLW) 對麻醉後兔子奧迪氏括約肌相位收縮壓力（PP）之變化統計圖 57
【圖4.16】 澱粉（Starch）對麻醉後兔子奧迪氏括約肌壓力圖之變化 59
【圖4.17】 澱粉（Starch）對麻醉後兔子奧迪氏括約肌基礎壓力（TP）之變化統計圖 60
【圖4.18】 澱粉（Starch）對麻醉後兔子奧迪氏括約肌相位收縮壓力（PP）之變化統計圖 61
【圖4.19】 二次水（2nd H2O）對麻醉後兔子奧迪氏括約肌壓力圖之變化 62
【圖4.20】 二次水（2nd H2O）對麻醉後兔子奧迪氏括約肌基礎壓力（TP）之變化統計圖 63
【圖4.21】 二次水（2nd H2O）對麻醉後兔子奧迪氏括約肌相位收縮壓力（PP）之變化統計圖 64
【圖4.22】 事先施予A.P.P對木香檳榔丸1.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌壓力圖之變化 65
【圖4.23】 事先施予A.P.P對木香檳榔丸1.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌基礎壓力（TP）之變化統計圖 66
【圖4.24】 事先施予A.P.P對木香檳榔丸1.0g (MSBLW) 對麻醉後兔子奧迪氏括約肌相位收縮壓力（PP）之變化統計圖 67
【圖4.25】 事先施予Pirenzepine對木香檳榔丸1.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌壓力圖之變化 68
【圖4.26】 先施予Pirenzepine對木香檳榔丸1.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌基礎壓力（TP）之變化統計圖 69
【圖4.27】 先施予Pirenzepine對木香檳榔丸1.0gm (MSBLW) 對麻醉後兔子奧迪氏括約肌相位收縮壓力（PP）之變化統計圖 70
表目錄
【表3.1】木香檳榔丸（MUH SHIANG BIN LANG WAN）科學濃縮中藥處方成份表 27
【表4.1】膽囊（GB）、奧迪氏括約肌（SO）及十二指腸（Duodenum） 染色正反應結果百分比評分表 40
【表4.2】木香檳榔丸0.25 gm (MSBLW) 對麻醉後兔子奧迪氏括約肌之影響 46
【表4.3】木香檳榔丸0.5 gm (MSBLW) 對麻醉後兔子奧迪氏括約肌之影響 49
【表4.4】木香檳榔丸1.0 gm (MSBLW) 對麻醉後兔子奧迪氏括約肌之影響 52
【表4.5】木香檳榔丸2.0 gm (MSBLW) 對麻醉後兔子奧迪氏括約肌之影響 55
【表4.6】澱粉（Starch）對麻醉後兔子奧迪氏括約肌之影響 59
【表4.7】二次水（2nd H2O）對麻醉後兔子奧迪氏括約肌之影響 62
【表4.8】事先施予A.P.P對木香檳榔丸1.0 gm (MSBLW) 麻醉後兔子奧迪氏括約肌之影響 65
【表4.9】事先施予Pirenzepine對木香檳榔丸1.0 gm (MSBLW) 麻醉後兔子奧迪氏括約肌之影響 68

參考文獻
1. Chiu JH, Kuo YL, Lui WY, Wu CW and Hong CY: Somatic Electrical Nerve Stimulation Regulates the Motility of Sphincter of Oddi in Rabbits and Cats Evidence for a Somatovisceral Reflex Mediated by Cholecystokinin. Digest Dis Sci, 44:1759-67, 1999.
2. Chiu JH, Chen YL, Lui WY and Hong CY: Local heat stimulates nitric oxide synthesis as a mediator for the neural relaxation of the feline sphincter of Oddi. Life Sci, 63:413-28, 1998
3. 清, 汪昂, 醫方集解, 昭人出版社, 台中, pp90-91, 1979
4. Oddi RD: Disposition a sphincter speciae de I'ouverture du canal choledoque. Arch Ital Biol, 8:317-22, 1887
5. Hendrickson WF. A study of the musculative of the entire extrahepatic biliary system, including that of the duodenal portion of the common bile duct and of the sphincter. Johns Hopkins Hosp Bull, 9:221-32, 1898
6. Funch-Jensen P. EbbehØj N：Sphincter of oddi motility. Scand J Gastroentero, 31Supple 216:46-51, 1996
7. Boyden EA: The sphincter of Oddi in man and certain representative mammals. Surgery, 1:25-37, 1937
8. Teilum D: In vitro measurement of the length of the sphincter of Oddi. Endoscopy, 1:114-6, 1991
9. Tooali J: Sphincter of Oddi motility. Br J Surg, 71:251-6, 1984
10.Ono K, Watanabe N, Suzaki K, Tsuschida H, Sugiyama Y and Abo M. Bile flow mechanism in man. Arch Surg, 96:869-74, 1968
11.Sarles JC, Bidart JM and Devaux MA: Action of cholecystokinin and caerulein on the rabbit sphincter of Oddi. Digestion, 14:415-23, 1976
12.Toouli J, Dodds WJ, Honda R, Sarna S, Hogan WJ, Komarowstki RA, Linehan JH and Arndorfer RC. Motor function of the oppossum sphincter of Oddi. J Clin Invest, 71:208-20, 1983
13.Sarles JC, Delecourt P, Castello H, Gaeta L, Nacchiero M, Amoros JP, Devaus MA, Award R: Active of gastrointestinal hormones on the myoelectric activity of the sphincter of Oddi in living rabbit. Regul Peptides, 2:114-24, 1981
14.Coruzzi G, Adami M and Bertaccini G : Gastric antisecretory activity of telenzepine , a new M1-selective muscarinic antagonist : comparison with pirenzepine. Arch Int Pharmacod T, 302:232-41, 1989
15.Micheletti R, Schiavone A, Angelici O, Duranti P, Giudici L, Cereda E and Donetti A. Affinity profile of the novel muscarinic antagonist, guanylpirenzepine. Life Sci, 47:PL55-8, 1990
16.Persson CGA. Adrenoreceptor functions in the cat choledochoduodenal junction in vitro. Br J Pharmacol, 42:447-61, 1971
17.Takahashi I, Dodds WJ, Hogan WJ, Itoh Z and Baker K: Effect of vagotomy on biliary-tract motor activity in the opossum. Digest Dis Sci, 33:481-9, 1988
18.Burnstock G: Post and correct evidence for the perinergic nerve hypothesis. In Physiological and Regulatory functions of Adenosine and Adenine Nucleotides, ed. By Baer HP and Drummond GI, Raven Press, New York pp 2-32, 1979
19.Gillespie, J.S.: Non-adrenergic non-cholinergic inhibitory control of gastrointestinal motility. In Motility of the Digestive Tract. ed by Wienbeck M, Raven Press, New York, pp 51-66, 1982
20.Vanderwinden JM, Mailleus P, Schiffmann SN, Vandershaeghen JJ and De L MH: Nitric oxide synthase activity in infantile hypertrophic phloric stenosis. New Engl J Med, 327: 515-7, 1992
21.Pauletzki JG, Sharkey KA, Davison JS, Bomzon A and Shaffer EA: Involvement of L-arginine-nitric oxide pathways in neural relaxation of the sphincter of Oddi. Eur J Pharmacol, 232:263-70, 1993
22.Mourelle M, Guarner, Moncada S and Malagelada JR: The arginine/nitric oxide pathway modulates sphincter of Oddi motor activity in guinea pigs and rabbits. Gastroenterology, 105:1299-305, 1993
23.Kaufman HS, Shermak MA, May CA, Pitt HA and Lillemoe KD: Nitric oxide inhibits resting sphincter of Oddi activity. Am J Surg, 165:74-80, 1993
24.Han JS, Wang Q: Mobilization of specific neuropeptides by peripheral stimulation of identified frequencies. NIPS, 7:176-80, 1992
25.Larsson LI, Childers S, Snyder SH: Met- and Leu-enkephalin immunoreactivity in separate. Neurones, 282:407-10, 1979
26.Behar J, Biancani P: Neural control of the sphincter of Oddi: Phsiologic role of enkaphalins on the regulation of basal sphincter of oddi motor activity in the cat. Gastroenterology, 86:134-41, 1984
27.Han JS, Ding XZ and Fan SG: The frequency as the cardinal determinant for electroacupuncture analgesia to be reversed by naloxone. Acta Physiol Sin, 38:475-82,1986
28.Sarles JC: Hormonal control of sphincter of Oddi. Digest Dis Sci, 31:208-12, 1986
29.Grider JR: Role of cholecystokinin in the regulation of gastrointestinal motility. J Nutr, 124:1334S-9S, 1994
30.Dahlstrand C, Dahlström A, Theodorsson E, Rehfeld J and Ahlman H: Is the CCK-8 induced relaxation of the feline sphincter of Oddi mediated by VIP neurons? J Autonom Nerv syst, 31: 75-84, 1990
31.Behar J and Biancani P: Pharmacologic Characterization of excitatory and inhibitory cholecystokinin receptors of the cat gallbladder and sphincter of Oddi. Gastroenterology, 92:764-70, 1987
32.Liddle RA: Cholecystokinine cells. Annu Rev Physiol, 59:221-42, 1997
33.Corp EC, Curcio M, Gibbs J and Smith GP: The effect of centrally administered CCK-receptor antagonists on food intake in rats. Physiol Behav, 61:823-7, 1997
34.Faris PL, Komisaruk BR, Watkins LR, Mayer DJ: Evidence for the neuropeptide cholecystokinin as an antagonist of opiate analgesia. Science, 219:310-2,1983
35.Han JS, Tang J, Huang BS, Liang XN, Zhang WQ: Acupuncture tolerance in rats: anti-opiate substrates implicated. Chin Med J-Peking 92:625-7, 1979
36.Wiley JW, O’Dorisio TM and Owyang C: Vasoactive intestinal polypeptide mediates cholecystokinin-induced relaxation of the sphincter of Oddi. J Clin Invest, 81:1920-4, 1988
37.Alumets J, Schaffalitzky De Muckadell O, Fahrenkrug J, Sundler F, Hakanson R, Uddman R: A rich VIP nerve supply is characteristic of sphincters. Nature, 280:155-6, 1979
38.Dahlstrand C, Theodorsson E, Dahlström A and Ahlman H: VIP antisera inhibit the relaxatory motor respone of feline sphincter of Oddi and gallbladder induced by VIP or vagal nerve stimulation. Acta Physcol Scand, 137:375-8, 1989
39.Guelrud M, Rossiter A, Souney PF, Mendoza S and Mujica V: The effect of transcutaneous nerve stimulation on sphincter of Oddi Pressure in Patients with Biliary Dyskinesia. Am J Gastroenterol, 86: 581-5, 1991
40.Grider JR, Murthy KS, Jin JG and Makhlouf GM: Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release. Am J Physiol, 262:G774-8, 1992
41.Wyatt AP: The relationship of the sphincter of Oddi to the stomach, duodenum and gall-bladder. Am J Physiol, 193:225-43, 1967
42.Thune A, Thornell E and Svanvik J. Reflex regulation of flow resistance in the feline sphincter of Oddi by hydrostatic pressure in the biliary tract. Gastroenterology, 91 1364-9, 1986
43.Thune A, Saccone GTP, Scicchitano JP and Toouli J: Distension of the gallbladder inhibits sphincter of Oddi motility in man. Gut, 32:692-3, 1991
44.Steinberg WM: Sphincter of Oddi dysfunction: A clinical controversy. Gastroenterology, 95:1409, 1988
45.Acosta JM and Ledesma CL：Gallstone migration as a cause of acute pancreatitis. New Engl J Med, 290:484, 1974
46.Hogan WJ, Geenen JE: Biliary dyskinesia. Endoscopy, 20:179, 1988
47.林昭庚, 新針灸大成, 中國醫藥大學針灸研究中心出版, 台中, pp655, 1993
48.林昭庚, 新針灸大成, 中國醫藥大學針灸研究中心出版, 台中, pp671, 1993
49.黃維三, 針灸科學, 國立編譯館出版, 臺北, pp519, 1985
50.Dal Monte PR, D'imperio M, Ferri M, Fratucello F and del Soldato P: A combination of pirenzepine and cimetidine: a new approach to tretment of duodenal ulcer in 'non-responders'. Hepato-gastroenterol, 32:126-8, 1985
51.Bardhan KD, Thompson M, Bose K, Hinchliffe RFC, Crowe J, Weir DG, Mccarthy C, Walters J, Thomson TJ, Thomson MH, Gait JE, King C and Prudham D: Combined anti-muscarinic and H2 receptor blockade in the healing of refractory duodenal ulcer. A double blind study. Gut, 28:1505-9, 1987
52.Thune A, Jivegard L, Svanvik J: Flow resistance in the choledocho- duodenal sphincter as studied by constant-pressure and constant- perfusion techniques. Acta Physiol Scand, 135:279-84, 1989
53.Fass J, Bares R, Hermsdorf V, Schumpelick V. Effect of intravenous ketamine on gastrointestinal motility in the dog. Intens Care Med, 21:584-9, 1995
54.Sulli JP, Mehmet CO, Peggy G, Antorine F and Dennis FK: Comparison of xylazine with tiletamine-zolazepam (Telazol) and xylazine-ketamine anesthesia in rabbits. Lab Anim Sci, 41: 51-3, 1991
55.Marini RP, Avison DL, Corning BF and Lipman NS: Ketamine/ Xylazine/ Butorphanol: A new aneathetic combination for rabbits. Lab Anim Sci, 42:57-62, 1992
56.Lipman NS, Marini RP and Erdman SE: A comparison of ketamine/ xylazine and ketamine/ xylazine/ acepromazine anesthesia in the rabbit. Lab Anim Sci, 40:395-8, 1990.
57.Jefferey DW, Roland AWS and Mary ER: The effects of prolonged ketamine-xylazine introvenous infusion on arterial blood pH, blood gases, mean arterial blood 4 pressure, heart and respiratory rates, rectal temperature and reflexes in the rabbit. Lab Anim Sci, 39: 411-6, 1989
58.Bymaster FP, McKinzie DL, Felder CC, Wess J: Use of M1-M5 muscarinic receptor knockout mice as novel tools delineate the physiological roles of the muscarinic choloinergic system. Neurochem Res, 28：437-42, 2003
59.江蘇新醫學院, 中藥大辭典, 上海科學技術出版社, 上海, pp2525-8, 1991
60.Ghelardini C, Galeotti N, Lelli C, Bartolini A: M1 receptor activation is a requirement for arecoline analgesia. Farmaco, 56: 383-5, 2001
61.Eltze M, Konig H, Ullrich B, Grebe T：Contraction of guinea-pig gallbladder muscarinic M3 or M4 receptor? Euo J Pharmacol, 332: 77-87, 1997