跳到主要內容

臺灣博碩士論文加值系統

(44.221.70.232) 您好!臺灣時間:2024/05/21 06:54
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

我願授權國圖
: 
twitterline
研究生:吳靜玉
研究生(外文):Ching-Yu Wu
論文名稱:大鼠紋狀體區單胺類神經傳遞物質及其代謝物生體濃度監測方法之開發
論文名稱(外文):Development of in situ for method for monitoring monoamine neurotransmitter and metabolite levels in rat corpus striatum
指導教授:劉國盛
指導教授(外文):Kuo-Sheng Liu
學位類別:碩士
校院名稱:嘉南藥理科技大學
系所名稱:藥物科技研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2010
畢業學年度:98
語文別:中文
論文頁數:76
中文關鍵詞:高效能液相層析-電化學偵測器紋狀體區微透析嗎啡
外文關鍵詞:HPLC-ECDCorpus striatumMicrodialysisMorphine
相關次數:
  • 被引用被引用:0
  • 點閱點閱:269
  • 評分評分:
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
本研究以探討微透析技術在大鼠腦中紋狀體區進行取樣,以利用高效能液相層析-電化學偵測器同時偵測神經傳遞物質及其代謝物含量之變化。其微透析管總長為14mm,膜長為4mm,透析膜材質為poly-arylethersulfone (PAES),可通透之最大分子量為2000 Daltons,本實驗在高效能液相層析-電化學偵測器條件使用包含C18 ODS-3μm 100 mm × 4.6 mm之層析管柱,移動相為91:9(v/v)之0.05M磷酸緩衝液(包含0.2mM sodium octyl sulfonate及0.05mM Na2EDTA,以磷酸調至pH=3)與甲醇,流速為1 ml/min,樣品注入量為20μl,電化學偵測器主要以石墨工作電極,銀/氯化銀為參考電極,電位設定在+0.6伏特。
本研究順利開發一個簡單高效能液相層析-電化學偵測器之方法可同時偵測單胺類神經傳遞物質及其代謝物,其最低偵測極限範圍為0.3-127nM,線性迴歸曲線之r2在0.99以上,而利用此分析方法結合微透析技術,觀察大鼠在急性、慢性嗎啡注射之不同狀態下腦部之紋狀體核區神經傳遞物質及其代謝物濃度之變化情形。
This study combined microdialysis sampling with high performance liquid chromatography-electrochemical detection (HPLC-ECD) for the determination of the monoamine neurotransmitters and metabolite levels in the rat corpus striatum.
The material of probe membrane (length 4mm) was poly- arylethersulfone (PAES) and the cut-offs of these membranes were 20,000 Daltons. Separation of the monoamine neurotransmitters was obtained by a C18 ODS-3μm 100 mm × 4.6 mm column at a mobile phase consisting of 9% methanol in buffer (0.2mM sodium octyl sulfonate (SOS) and 0.05mM ethylene diamine tetraacetic acid disodium salt (EDTA Na2) with phosphoric acid to pH of 3), operated at a flow rate of 1ml/min and a inject volume of 20μl .A potential seep of +0.6V was applied across the working and reference electrodes of the detector.
A Simple high-performance liquid chromatography with electrochemical detection using microdialysis was developed for simultaneous determination of monoamine neurotransmitters and metabolite levels in the rat corpus striatum. The detection limits of these compounds were 0.3~127nM, the correlation coefficients of regression were more than 0.99.
The method has been successfully applied to measure the neurotransmitters and their metabolite levels in the rat corpus striatum by morphine injection in acute and chronic morphine treatment.
中文摘要 I
Abstract II
致謝 IV
目錄 VI
表目錄 IX
圖目錄 X
第一章 緖論 1
第一節 研究動機與目的 1
第二章 文獻回顧 4
第一節 嗎啡介紹 4
壹、簡介 4
貳、類鴉片接受器之分類及作用 5
參、嗎啡之耐受性與依賴性 6
第二節 單胺類神經傳遞物質 9
壹、單胺類神經系統之簡介 9
貳、嗎啡依賴及戒斷可能牽涉神經作用之機轉 13
參、神經傳遞物質分析方法之發展 15
第三節 微透析 18
壹 微透析的介紹 18
貳 微透析之設計概念 18
參 微透析的原理 21
肆 微透析管 23
伍 微透析管使用及保存 25
陸 微透析薄膜 25
柒 微透析取樣的特色及優點 26
第三章 實驗設備、材料與方法 29
第一節 試藥與試劑 29
壹、標準品 29
貳、高效液相層析緩衝溶劑試藥 29
參、麻醉試藥 30
肆、透析液試藥 30
第二節 實驗設備 31
第三節. 實驗動物 33
第四節 動物模式之建立 33
第五節. 給藥模式 34
第六節 透析液之收集與分析 35
第七節 高效能液相層析法 35
壹、分析物質之電位偵測 35
貳、高效能液相層析之分析條件 35
參、校正曲線的建立 36
肆、偵測極限的測定及分析方法之確效 36
第八節 微透析探針的回收率 36
第四章 結果與討論 39
第一節 分析方法之建立 39
壹、神經傳遞物質之氧化電位偵測 39
貳、層析圖譜及條件探討 40
參、校正曲線的建立 40
肆、管柱之滯留時間及可測得之最低定量濃度 41
第二節 體外與體內神經傳遞物質之測定 48
壹、微透析管體外神經傳遞物質回收率 48
貳、體內神經傳遞物質之測定 50
第五章 結論 57
第六章 參考文獻 58
1.Contreras E, Tamayo L, Quijada L. Effects of tricyclic compounds and other drugs having a membrane stabilizing action on analgesia, tolerance to and dependence on morphine. Arch Int Pharmacodyn Ther. 1977;228(2):293-299.
2.Narita M, Yajima Y, Suzuki T. A new turn of research for morphine dependence. Nihon Arukoru Yakubutsu Igakkai Zasshi. 2000;35(5):283-294.
3.Mamiya T, Noda Y, Ren X, et al. Morphine tolerance and dependence in the nociceptin receptor knockout mice. J Neural Transm. 2001;108(12):1349-1361.
4.Narita M, Funada M, Suzuki T. Regulations of opioid dependence by opioid receptor types. Pharmacol Ther. 2001;89(1):1-15.
5.http://www.antidrug.nat.gov.tw. 行政院管制藥品管理局.
6.Pinelli A, Trivulzio S. Quantitative evaluation of opioid withdrawal signs in rats repeatedly treated with morphine and injected with naloxone, in the absence or presence of the antiabstinence agent clonidine. J Pharmacol Toxicol Methods. 1997;38(3):117-131.
7.Ghosh S, Grasing K. Presynaptic dopaminergic function in the nucleus accumbens following chronic opiate treatment and precipitated withdrawal. Neurochem Res. 1999;24(1):95-107.
8.el-Kadi AO, Sharif SI. The role of 5-HT in the expression of morphine withdrawal in mice. Life Sci. 1995;57(5):511-516.
9.Pinelli A, Trivulzio S, Ciapponi PM. Quantitative opioid withdrawal signs in rats: effects exerted by clothiapine administration. Fundam Clin Pharmacol. 1997;11(4):346-355.
10.Tallent M, Dichter MA, Bell GI, Reisine T. The cloned kappa opioid receptor couples to an N-type calcium current in undifferentiated PC-12 cells. Neuroscience. 1994;63(4):1033-1040.
11.Caille S, Rodriguez-Arias M, Minarro J, Espejo EF, Cador M, Stinus L. Changes in dopaminergic neurotransmission do not alter somatic or motivational opiate withdrawal-induced symptoms in rats. Behav Neurosci. 2003;117(5):995-1005.
12.Kadi AO, Sharif SI. The role of 5-HT in the expression of morphine withdrawal in mice. Life Sci. 1995;57(5):511-516.
13.Harrison LM, Kastin AJ, Zadina JE. Opiate tolerance and dependence: receptors, G-proteins, and antiopiates. Peptides. 1998;19(9):1603-1630.
14.Klockgether-Radke AP. Serturner and the discovery of morphine. 200 years of pain therapy with opioids. Anasthesiol Intensivmed Notfallmed Schmerzther. 2002;37(5):244-249.
15.Page JE. Silencing nature''s narcotics: metabolic engineering of the opium poppy. Trends Biotechnol. 2005;23(7):331-333.
16.Jaffe JH, O''Keeffe C. From morphine clinics to buprenorphine: regulating opioid agonist treatment of addiction in the United States. Drug Alcohol Depend. 2003;70(2):3-11.
17.Punch LJ, Self DW, Nestler EJ, Taylor JR. Opposite modulation of opiate withdrawal behaviors on microinfusion of a protein kinase A inhibitor versus activator into the locus coeruleus or periaqueductal gray. J Neurosci. 1997;17(21):8520-8527.
18.Goodman RR, Snyder SH, Kuhar MJ, Young WS, 3rd. Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography. Proc Natl Acad Sci U S A. 1980;77(10):6239-6243.
19.Morris BJ, Herz A. Autoradiographic localization in rat brain of kappa opiate binding sites labelled by [3H]bremazocine. Neuroscience. 1986;19(3):839-846.
20.Werling LL, Frattali A, Portoghese PS, Takemori AE, Cox BM. Kappa receptor regulation of dopamine release from striatum and cortex of rats and guinea pigs. J Pharmacol Exp Ther. 1988;246(1):282-286.
21.Quirion R, Zajac JM, Morgat JL, Roques BP. Autoradiographic distribution of mu and delta opiate receptors in rat brain using highly selective ligands. Life Sci. 1983;33 (1):227-230.
22.Brody L, Minneman 原著;廖志飛編譯. 最新人體藥理學. 2000.
23.Raisch DW, Fye CL, Boardman KD, Sather MR. Opioid dependence treatment, including buprenorphine/naloxone. Ann Pharmacother. 2002;36(2):312-321.
24.Pletscher A. Regulation of catecholamine turnover by variations of enzyme levels. Pharmacol Rev. 1972;24(2):225-232.
25.Liu YL, Cheng AT, Chen HR, Hsu YP. Simultaneous HPLC of twelve monoamines and metabolites shows neuroblastoma cell line releases HVA and HIAA. Biomed Chromatogr. 2000;14(8):544-548.
26.Javelle N, Renaud B, Lambas-Senas L. Monoamine metabolism in the locus coeruleus measured concurrently with behavior during opiate withdrawal: an in vivo microdialysis study in freely moving rats. J Neurochem. 1997;68(2):683-690.
27.Shippenberg TS, Elmer GI. The neurobiology of opiate reinforcement. Crit Rev Neurobiol. 1998;12(4):267-303.
28.David V, Durkin TP, Cazala P. Differential effects of the dopamine D2/D3 receptor antagonist sulpiride on self-administration of morphine into the ventral tegmental area or the nucleus accumbens. Psychopharmacology. 2002;160(3):307-317.
29.Gysling K, Wang RY. Morphine-induced activation of A10 dopamine neurons in the rat. Brain Res. 1983;277(1):119-127.
30.Di Chiara G, Imperato A. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A. 1988;85(14):5274-5278.
31.Harris GC, Aston-Jones G. Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome. Nature. 1994;371(6493):155-157.
32.Wang G, Vincent M, Rodrigues W, et al. Development and GC-MS validation of a highly sensitive recombinant G6PDH-based homogeneous immunoassay for the detection of buprenorphine and norbuprenorphine in urine. J Anal Toxicol. 2007;31(7):377-382.
33.Okada M, Mine K, Noda T, Kataoka Y, Nakagawa T. Simultaneous determination of noradrenaline and 3-methoxy-4-hydroxyphenylglycol in plasma with high-performance liquid chromatography using electrochemical detection. Anal Biochem. 1988;175(2):562-568.
34.Hashimoto Y, Nago S, Tsunekawa M, Shibakawa K, Miyata Y. Validation of HPLC-UV methods for quantitatively determining landiolol and its major metabolite in human blood. Biol Pharm Bull. 2009;32(1):121-125.
35.Fujino K, Yoshitake T, Kehr J, Nohta H, Yamaguchi M. Simultaneous determination of 5-hydroxyindoles and catechols by high-performance liquid chromatography with fluorescence detection following derivatization with benzylamine and 1,2-diphenylethylenediamine. J Chromatogr A. 2003;1012(2):169-177.
36.Lacassie E, Gaulier JM, Marquet P, Rabatel JF, Lachatre G. Methods for the determination of seven selective serotonin reuptake inhibitors and three active metabolites in human serum using high-performance liquid chromatography and gas chromatography. J Chromatogr B Biomed Sci Appl. 2000;742(2):229-238.
37.林宗義 儀器分析. 美亞書版股份有限公司. 1994.
38.http://www.microdialysis.se.
39.Merbel NC. Membrane-based sample preparation coupled on-line to chromatography or electrophoresis. J Chromatogr A. 1999;856(1-2):55-82.
40.Yang H, Peters JL, Allen C, Chern SS, Coalson RD, Michael AC. A theoretical description of microdialysis with mass transport coupled to chemical events. Anal Chem. 2000;72(9):2042-2049.
41.Jonsson JA, Mathiasson L. Membrane-based techniques for sample enrichment. J Chromatogr A. 2000;902(1):205-225.
42.Thomas FH. HANDBOOK OF MICRODIALYSIS. Handbook of Behavioral Nenroscience. 2007;16.
43.Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates, 2nd edn. Academic Press Inc. 1986.
44.Rosenbloom AJ, Sipe DM, Weedn VW. Microdialysis of proteins: performance of the CMA/20 probe. J Neurosci Methods. 2005;148(2):147-153.
45.Sanchez A, Toledo-Pinto EA, Menezes ML, Pereira OC. A simple high-performance liquid chromatography assay for on-line determination of catecholamines in adrenal gland by direct injection on an ISRP column. Pharmacol Res. 2004;50(5):481-485.
46.Chan EC, Wee PY, Ho PC. Evaluation of degradation of urinary catecholamines and metanephrines and deconjugation of their sulfoconjugates using stability-indicating reversed-phase ion-pair HPLC with electrochemical detection. J Pharm Biomed Anal. 2000;22(3):515-526.
47.Yoshitake T, Iizuka R, Kehr J, Nohta H, Ishida J, Yamaguchi M. Determination of serotonin in microdialysis samples from rat brain by microbore column liquid chromatography with post-column derivatization and fluorescence detection. J Neurosci Methods. 2001;109(2):91-96.
48.Ventura R, Morrone C, Puglisi-Allegra S. Prefrontal/accumbal catecholamine system determines motivational salience attribution to both reward- and aversion-related stimuli. Proc Natl Acad Sci U S A. 2007;104(12):5181-5186.
49.Xu F, Gao M, Wang L, Jin L. Study on the effect of electromagnetic impulse on neurotransmitter metabolism in nerve cells by high-performance liquid chromatography-electrochemical detection coupled with microdialysis. Anal Biochem. 2002;307(1):33-39.
50.Szemeredi K, Komoly S, Kopin IJ, Bagdy G, Keiser HR, Goldstein DS. Simultaneous measurement of plasma and brain extracellular fluid concentrations of catechols after yohimbine administration in rats. Brain Res. 1991;542(1):8-14.
51.Huang NK, Tseng CJ, Wong CS, Tung CS. Effects of acute and chronic morphine on DOPAC and glutamate at subcortical DA terminals in awake rats. Pharmacol Biochem Behav. 1997;56(3):363-371.
52.Enrico P, Esposito G, Mura MA, et al. Effect of morphine on striatal dopamine metabolism and ascorbic and uric acid release in freely moving rats. Brain Res. 1997;745(1-2):173-182.
53.Tokuyama S, Wakabayashi H, Hoskins B, Ho IK. Naloxone-precipitated changes in biogenic amines and their metabolites in various brain regions of butorphanol-dependent rats. Pharmacol Biochem Behav. 1996;54(2):461-468.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關論文