跳到主要內容

臺灣博碩士論文加值系統

(18.205.192.201) 您好!臺灣時間:2021/08/05 03:50
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

: 
twitterline
研究生:韋妮可
研究生(外文):Wei, Niko
論文名稱:血清素神經活性在經抑鈣素治療之去卵巢引起痛覺敏感大鼠的研究
論文名稱(外文):Investigation Of Brain Serotonin Neuron Activity In Calcitonin-Treated Ovariectomized Hyperalgesic Rats
指導教授:徐佳福
指導教授(外文):Shyu, Jiafwu
口試委員:馬國興葉啟斌周元華
口試委員(外文):Ma, KuohsingYeh, ChinbinChou, Yuanhwa
口試日期:2012-05-28
學位類別:碩士
校院名稱:國防醫學院
系所名稱:生物及解剖學研究所
學門:生命科學學門
學類:生物訊息學類
論文種類:學術論文
論文出版年:2013
畢業學年度:100
語文別:中文
論文頁數:58
中文關鍵詞:血清素抑鈣素去卵巢大鼠
外文關鍵詞:serotonincalcitoninovariectomized ratbrain
相關次數:
  • 被引用被引用:0
  • 點閱點閱:204
  • 評分評分:
  • 下載下載:14
  • 收藏至我的研究室書目清單書目收藏:0
抑鈣素是一種由甲狀腺濾泡旁細胞所製造的多肽荷爾蒙。抑鈣素能夠降低血鈣濃度及抑制骨中破骨細胞的活性,因為這些特性,抑鈣素被拿來治療高血鈣症及停經後骨質疏鬆症。在臨床上也被觀察並報導出抑鈣素具有鎮痛效果,但是詳細的機制尚未明瞭。而有研究指出抑鈣素的鎮痛效果可能是透過下行抑制性血清素系統的參與所產生。大鼠分為四個組別:OVX-CT、OVX-SDCP、OVX-con、sham-con。利用新發展出的18-F標定正子斷層照影放射性配體進行各組活體大鼠腦中血清素轉運體(SERT)活性。犧牲之後,保留大鼠腦部及血液並進行血清素神經免疫組織化學染色、SERT西方點墨法。根據正子斷層照影分析結果,OVX-con組的SERT比值在皮質、紋狀體、海馬迴降低,在丘腦、下丘腦及中腦增加。OVX-CT組在六個區域的SERT比值皆降低。根據西方點墨法分析結果,OVX-con組的SERT表現量在皮質、腦幹降低,在中腦增加。OVX-CT組SERT表現量在皮質、中腦、腦幹皆為增加。血清素神經纖維密度分析結果顯示,OVX-con組大鼠腦的神經纖維密度在皮質、海馬迴、紋狀體、丘腦、下丘腦、背核皆為降低。未來實驗將增加樣本數量並統計分析來確認抑鈣素是否會對去卵巢大鼠腦部血清素神經系統造成影響。
Calcitonin is a polypeptide hormone that is produced by the parafollicular cells of thyroid gland. It acts to reduce blood calcium concentration and inhibit osteoclast activity in bones. Because of these features, clacitonin is used as a treatment of hypercalcaemia and postmenopausal osteoporosis. The analgesic effect of calcitonin has been observed and reported in clinical situations, but the mechanism is still unclear. Studies reported that the descending inhibitory serotonergic system may be involved in the analgesic mechanism of calcitonin. The purpose of this study is to evaluate the antinociceptive effect of calcitonin by investigating serotonin activity in the brain of ovariectomized rats. Rats were divided into four groups: OVX-CT, OVX-SDCP, OVX-con and sham-con groups. For each group evaluate their serotonin transporter (SERT) activity in the living rat brain were evaluated with newly developed 18F-labeled PET radioligand. After sacrified, we reserved brains and collected blood. Immunohistochemical stain of serotonin neuron, SERT western blot were performed. According to the result of PET image, OVX-con group showed that SERT ratio decreased in cortex, striatum and hippocampus, and increased in thalamus, hypothalamus and midbrain. OVX-CT Group showed decrease SERT ratio in all six regions. In Western blot analysis, OVX-con group SERT expression decreased in cortex and brainstem, and increased in midbrain. OVX-CT group showed decreased SERT expression in all three regions. Analysis of serotonin fiber density, OVX-con showed lower fibers density than sham in cortex, hippocampus, striatum, thalamus, hypothalamus and raphe. In the future, we will increase sample number and analysis statistically to confirm whether calcitonin affect serotonin system of ovariectomized rats in the brain.

正文目錄............................................................................2
圖目錄..............................................................................5
中文摘要............................................................................6
英文摘要............................................................................7
第一章 緒言..........................................................................8
第一節 抑鈣素
壹、歷史背景......................................................................8
貳、抑鈣素的鎮痛作用...............................................................9
參、抑鈣素的鎮痛機制假說...........................................................10
肆、抑鈣素對血清素神經系統的影響.....................................................13
第二節 血清素神經系統.................................................................15
壹、血清素之功能..................................................................15
貳、血清素合成作用機轉.............................................................15
參、血清素轉運體..................................................................17
第三節 研究動機與目的.................................................................19
第二章 材料與方法....................................................................20
第一節 實驗材料與藥品.................................................................20
第二節 藥品與其他溶液之配製............................................................22
第三節 實驗方法......................................................................24
第三章 結果..........................................................................31
第一節 比較4-18F-ADAM在假手術(sham)、去卵巢(OVX)、去卵巢後給予抑鈣素(OVX-CT)、
去卵巢後給予雙磷酸鹽類藥物(OVX-SDCP)之大鼠腦部其造影活性............................31
第二節 比較在sham、OVX、OVX-CT、OVX-SDCP大鼠在大腦皮質、中腦、腦幹之SERT表現量...............33
第三節 利用SPECT造影比較123I-ADAM在sham、OVX、OVX-CT、OVX-ALE之大鼠腦部其造影活性...........34
第四節 比較在sham、OVX、大鼠在大腦皮質、紋狀體、中腦、腦幹之SERT表現量........................36
第五節 比較免疫組織化學染色在sham、OVX大鼠腦部血清素神經系統之變化............................37
第四章 討論..........................................................................38
第五章 結論..........................................................................42
第六章 參考文獻.......................................................................43
第七章 結果附圖.......................................................................46

1.Copp, D.H. and E.C. Cameron, Demonstration of a hypocalcemic factor (calcitonin) in commercial parathyroid extract. Science, 1961. 134(3495): p. 2038.
2.Azria, M., D.H. Copp, and J.M. Zanelli, 25 years of salmon calcitonin: from synthesis to therapeutic use. Calcif Tissue Int, 1995. 57(6): p. 405-8.
3.Siminoski, K. and R.G. Josse, Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 9. Calcitonin in the treatment of osteoporosis. CMAJ, 1996. 155(7): p. 962-5.
4.Patel, U., et al., Clinical profile of acute vertebral compression fractures in osteoporosis. Br J Rheumatol, 1991. 30(6): p. 418-21.
5.Lyritis, G.P., et al., Pain relief from nasal salmon calcitonin in osteoporotic vertebral crush fractures. A double blind, placebo-controlled clinical study. Acta Orthop Scand Suppl, 1997. 275: p. 112-4.
6.Pun, K.K. and L.W. Chan, Analgesic effect of intranasal salmon calcitonin in the treatment of osteoporotic vertebral fractures. Clin Ther, 1989. 11(2): p. 205-9.
7.Miralles, F.S., et al., Postoperative analgesia induced by subarachnoid lidocaine plus calcitonin. Anesth Analg, 1987. 66(7): p. 615-8.
8.Jaeger, H. and C. Maier, Calcitonin in phantom limb pain: a double-blind study. Pain, 1992. 48(1): p. 21-7.
9.Micieli, G., et al., Effectiveness of salmon calcitonin nasal spray preparation in migraine treatment. Headache, 1988. 28(3): p. 196-200.
10.Patti, F., et al., Calcitonin and migraine. Headache, 1986. 26(4): p. 172-4.
11.Tseng, L.F., H.H. Loh, and C.H. Li, Beta-Endorphin as a potent analgesic by intravenous injection. Nature, 1976. 263(5574): p. 239-40.
12.Laurian, L., et al., Calcitonin induced increase in ACTH, beta-endorphin and cortisol secretion. Horm Metab Res, 1986. 18(4): p. 268-71.
13.Pecile, A., et al., Effects of intracerebroventricular calcitonin in the conscious rabbit. Experientia, 1975. 31(3): p. 332-3.
14.Pecile, A., Calcitonin and relief of pain. Bone Miner, 1992. 16(3): p. 187-9.
15.Azria, M., Possible mechanisms of the analgesic action of calcitonin. Bone, 2002. 30(5 Suppl): p. 80S-83S.
16.Fischer, J.A., S.M. Sagar, and J.B. Martin, Characterization and regional distribution of calcitonin binding sites in the rat brain. Life Sci, 1981. 29(7): p. 663-71.
17.Sibilia, V., et al., Amylin compared with calcitonin: competitive binding studies in rat brain and antinociceptive activity. Brain Res, 2000. 854(1-2): p. 79-84.
18.Nakamoto, H., et al., Localization of calcitonin receptor mRNA in the mouse brain: coexistence with serotonin transporter mRNA. Brain Res Mol Brain Res, 2000. 76(1): p. 93-102.
19.Colado, M.I., et al., Involvement of central serotonergic pathways in analgesia elicited by salmon calcitonin in the mouse. Eur J Pharmacol, 1994. 252(3): p. 291-7.
20.Ito, A., et al., Mechanisms for ovariectomy-induced hyperalgesia and its relief by calcitonin: participation of 5-HT1A-like receptor on C-afferent terminals in substantia gelatinosa of the rat spinal cord. J Neurosci, 2000. 20(16): p. 6302-8.
21.Ormazabal, M.J., et al., Salmon calcitonin potentiates the analgesia induced by antidepressants. Pharmacol Biochem Behav, 2001. 68(1): p. 125-33.
22.Ormazabal, M.J., et al., Study of mechanisms of calcitonin analgesia in mice. Involvement of 5-HT3 receptors. Brain Res, 1999. 845(2): p. 130-8.
23.Shibata, K., et al., Ovariectomy-induced hyperalgesia and antinociceptive effect of elcatonin, a synthetic eel calcitonin. Pharmacol Biochem Behav, 1998. 60(2): p. 371-6.
24.Yoshimura, M., Analgesic mechanism of calcitonin. J Bone Miner Metab, 2000. 18(4): p. 230-3.
25.Takayama, B., et al., An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats. BMC Musculoskelet Disord, 2008. 9: p. 164.
26.Berger, M., J.A. Gray, and B.L. Roth, The expanded biology of serotonin. Annu Rev Med, 2009. 60: p. 355-66.
27.Fuller, R.W., Mechanisms and functions of serotonin neuronal systems: opportunities for neuropeptide interactions. Ann N Y Acad Sci, 1996. 780: p. 176-84.
28.Launay, J.M., et al., Serotonin receptors and therapeutics. Cell Mol Biol (Noisy-le-grand), 1994. 40(3): p. 327-36.
29.Nagai, S., Serotonin containing and histamine containing cells in human stomach. Identification of these cells by fluorescent microscope and electron microscope. Gastroenterol Jpn, 1976. 11(4): p. 363-73.
30.Joyce, J.N., The dopamine hypothesis of schizophrenia: limbic interactions with serotonin and norepinephrine. Psychopharmacology (Berl), 1993. 112(1 Suppl): p. S16-34.
31.Owens, M.J. and C.B. Nemeroff, Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem, 1994. 40(2): p. 288-95.
32.Olivier, B. and R. van Oorschot, 5-HT1B receptors and aggression: a review. Eur J Pharmacol, 2005. 526(1-3): p. 207-17.
33.Messing, R.B. and L.D. Lytle, Serotonin-containing neurons: their possible role in pain and analgesia. Pain, 1977. 4(1): p. 1-21.
34.Jacobs, B.L. and E.C. Azmitia, Structure and function of the brain serotonin system. Physiol Rev, 1992. 72(1): p. 165-229.
35.Walther, D.J., et al., Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science, 2003. 299(5603): p. 76.
36.Zhang, X., et al., Tryptophan hydroxylase-2 controls brain serotonin synthesis. Science, 2004. 305(5681): p. 217.
37.Hoyer, D., et al., International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin). Pharmacol Rev, 1994. 46(2): p. 157-203.
38.Peroutka, S.J., Molecular biology of serotonin (5-HT) receptors. Synapse, 1994. 18(3): p. 241-60.
39.Booij, J. and M.M. de Win, Brain kinetics of the new selective serotonin transporter tracer [(123)I]ADAM in healthy young adults. Nucl Med Biol, 2006. 33(2): p. 185-91.
40.Lin, K.J., et al., Brain SPECT imaging and whole-body biodistribution with [(123)I]ADAM - a serotonin transporter radiotracer in healthy human subjects. Nucl Med Biol, 2006. 33(2): p. 193-202.
41.Marcusson, J.O. and S.B. Ross, Binding of some antidepressants to the 5-hydroxytryptamine transporter in brain and platelets. Psychopharmacology (Berl), 1990. 102(2): p. 145-55.
42.Meltzer, C.C., et al., Serotonin in aging, late-life depression, and Alzheimer's disease: the emerging role of functional imaging. Neuropsychopharmacology, 1998. 18(6): p. 407-30.
43.Tibbles, P.M. and J.S. Edelsberg, Hyperbaric-oxygen therapy. N Engl J Med, 1996. 334(25): p. 1642-8.
44.Foreman, M.M., J.L. Hall, and R.L. Love, The role of the 5-HT2 receptor in the regulation of sexual performance of male rats. Life Sci, 1989. 45(14): p. 1263-70.
45.Sheward, W.J., E.M. Lutz, and A.J. Harmar, The expression of the calcitonin receptor gene in the brain and pituitary gland of the rat. Neurosci Lett, 1994. 181(1-2): p. 31-4.

QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊