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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林君榮 | |
| dc.contributor.author | Yi-Hsuan Peng | en |
| dc.contributor.author | 彭宜萱 | zh_TW |
| dc.date.accessioned | 2021-06-16T16:42:25Z | - |
| dc.date.available | 2017-09-19 | |
| dc.date.copyright | 2012-09-19 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-24 | |
| dc.identifier.citation | Amphoux, A., Vialou, V., Drescher, E. et al. (2006) Differential pharmacological in vitro properties of organic cation transporters and regional distribution in rat brain. Neuropharmacology, 50, 941-952.
Antkiewicz-Michaluk, L., Krygowska-Wajs, A., Szczudlik, A., Romanska, I. and Vetulani, J. (1997) Increase in salsolinol level in the cerebrospinal fluid of parkinsonian patients is related to dementia: advantage of a new high-performance liquid chromatography methodology. Biol Psychiatry, 42, 514-518. Booth, R. G., Castagnoli, N., Jr. and Rollema, H. (1989) Intracerebral microdialysis neurotoxicity studies of quinoline and isoquinoline derivatives related to MPTP/MPP+. Neurosci Lett, 100, 306-312. Brown, T. P., Rumsby, P. C., Capleton, A. C., Rushton, L. and Levy, L. S. (2006) Pesticides and Parkinson's disease--is there a link? Environ Health Perspect, 114, 156-164. Busch, A. E., Karbach, U., Miska, D. et al. (1998) Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol, 54, 342-352. Chen, Y. F., Wu, C. Y., Kirby, R., Kao, C. H. and Tsai, T. F. (2010) A role for the CISD2 gene in lifespan control and human disease. Ann N Y Acad Sci, 1201, 58-64. Cui, M., Aras, R., Christian, W. V. et al. (2009) The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway. Proc Natl Acad Sci U S A, 106, 8043-8048. Czlonkowska, A., Ciesielska, A., Gromadzka, G. and Kurkowska-Jastrzebska, I. (2006) Gender differences in neurological disease: role of estrogens and cytokines. Endocrine, 29, 243-256. Dahlin, A., Xia, L., Kong, W., Hevner, R. and Wang, J. (2007) Expression and immunolocalization of the plasma membrane monoamine transporter in the brain. Neuroscience, 146, 1193-1211. Dauphinee, S. M. and Karsan, A. (2006) Lipopolysaccharide signaling in endothelial cells. Lab Invest, 86, 9-22. DeCuypere, M., Lu, Y., Miller, D. D. and LeDoux, M. S. (2008) Regional distribution of tetrahydroisoquinoline derivatives in rodent, human, and Parkinson's disease brain. J Neurochem, 107, 1398-1413. Duan, H. and Wang, J. (2010) Selective transport of monoamine neurotransmitters by human plasma membrane monoamine transporter and organic cation transporter 3. J Pharmacol Exp Ther, 335, 743-753. Erickson, M. A. and Banks, W. A. (2011) Cytokine and chemokine responses in serum and brain after single and repeated injections of lipopolysaccharide: multiplex quantification with path analysis. Brain Behav Immun, 25, 1637-1648. Goto, M. (2008) Inflammaging (inflammation + aging): A driving force for human aging based on an evolutionarily antagonistic pleiotropy theory? Biosci Trends, 2, 218-230. Grundemann, D., Hahne, C., Berkels, R. and Schomig, E. (2003) Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther, 304, 810-817. Gulati, S. C., Sood, S. C., Bali, I. M. and Kak, V. K. (1980) Cerebral metabolism following brain injury. I. Acid-base and pO2 changes. Acta Neurochir (Wien), 53, 39-46. Haenisch, B. and Bonisch, H. (2010) Interaction of the human plasma membrane monoamine transporter (hPMAT) with antidepressants and antipsychotics. Naunyn Schmiedebergs Arch Pharmacol, 381, 33-39. Han, S. N. and Meydani, S. N. (2000) Antioxidants, cytokines, and influenza infection in aged mice and elderly humans. J Infect Dis, 182 Suppl 1, S74-80. Hindle, J. V. (2010) Ageing, neurodegeneration and Parkinson's disease. Age Ageing, 39, 156-161. Jonker, J. W. and Schinkel, A. H. (2004) Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). J Pharmacol Exp Ther, 308, 2-9. Koepsell, H. and Endou, H. (2004) The SLC22 drug transporter family. Pflugers Arch, 447, 666-676. Koepsell, H., Lips, K. and Volk, C. (2007) Polyspecific organic cation transporters: structure, function, physiological roles, and biopharmaceutical implications. Pharm Res, 24, 1227-1251. Koepsell, H., Schmitt, B. M. and Gorboulev, V. (2003) Organic cation transporters. Rev Physiol Biochem Pharmacol, 150, 36-90. Kortekaas, R., Leenders, K. L., van Oostrom, J. C., Vaalburg, W., Bart, J., Willemsen, A. T. and Hendrikse, N. H. (2005) Blood-brain barrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol, 57, 176-179. Kotake, Y., Sekiya, Y., Okuda, K. and Ohta, S. (2007) Cytotoxicity of 17 tetrahydroisoquinoline derivatives in SH-SY5Y human neuroblastoma cells is related to mitochondrial NADH-ubiquinone oxidoreductase inhibition. Neurotoxicology, 28, 27-32. Kotake, Y., Tasaki, Y., Makino, Y., Ohta, S. and Hirobe, M. (1995) 1-Benzyl-1,2,3,4-tetrahydroisoquinoline as a parkinsonism-inducing agent: a novel endogenous amine in mouse brain and parkinsonian CSF. J Neurochem, 65, 2633-2638. Kotake, Y., Yoshida, M., Ogawa, M., Tasaki, Y., Hirobe, M. and Ohta, S. (1996) Chronic administration of 1-benzyl-1,2,3,4-tetrahydroisoquinoline, an endogenous amine in the brain, induces parkinsonism in a primate. Neurosci Lett, 217, 69-71. Lee, W. K., Reichold, M., Edemir, B., Ciarimboli, G., Warth, R., Koepsell, H. and Thevenod, F. (2009) Organic cation transporters OCT1, 2, and 3 mediate high-affinity transport of the mutagenic vital dye ethidium in the kidney proximal tubule. Am J Physiol Renal Physiol, 296, F1504-1513. Lin, C. J., Tai, Y., Huang, M. T., Tsai, Y. F., Hsu, H. J., Tzen, K. Y. and Liou, H. H. (2010) Cellular localization of the organic cation transporters, OCT1 and OCT2, in brain microvessel endothelial cells and its implication for MPTP transport across the blood-brain barrier and MPTP-induced dopaminergic toxicity in rodents. J Neurochem, 114, 717-727. Liou, H. H., Hsu, H. J., Tsai, Y. F., Shih, C. Y., Chang, Y. C. and Lin, C. J. (2007) Interaction between nicotine and MPTP/MPP+ in rat brain endothelial cells. Life Sci, 81, 664-672. Lips, K. S., Luhrmann, A., Tschernig, T. et al. (2007) Down-regulation of the non-neuronal acetylcholine synthesis and release machinery in acute allergic airway inflammation of rat and mouse. Life Sci, 80, 2263-2269. Maeda, T., Oyabu, M., Yotsumoto, T., Higashi, R., Nagata, K., Yamazoe, Y. and Tamai, I. (2007) Effect of pregnane X receptor ligand on pharmacokinetics of substrates of organic cation transporter Oct1 in rats. Drug Metab Dispos, 35, 1580-1586. Maeda, T., Yotsumoto, T., Oyabu, M. and Tamai, I. (2008) Effect of glucocorticoid receptor ligand dexamethasone on the expression of organic cation transporter in rat liver. Drug Metab Pharmacokinet, 23, 67-72. Mark, L. (2004) Tetrahydroisoquinolines and Parkinson's Disease. In: Parkinson's Disease. CRC Press. Maruyama, W., Abe, T., Tohgi, H., Dostert, P. and Naoi, M. (1996) A dopaminergic neurotoxin, (R)-N-methylsalsolinol, increases in parkinsonian cerebrospinal fluid. Annals of Neurology, 40, 119-122. Maruyama, W., Sobue, G., Matsubara, K., Hashizume, Y., Dostert, P. and Naoi, M. (1997) A dopaminergic neurotoxin, 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, N-methyl(R)salsolinol, and its oxidation product, 1,2(N)-dimethyl-6,7-dihydroxyisoquinolinium ion, accumulate in the nigro-striatal system of the human brain. Neurosci Lett, 223, 61-64. Matsubara, K., Senda, T., Uezono, T. et al. (1998) Structural significance of azaheterocyclic amines related to Parkinson's disease for dopamine transporter. Eur J Pharmacol, 348, 77-84. Mayrand, R. R. and Levitt, D. G. (1983) Urea and ethylene glycol-facilitated transport systems in the human red cell membrane. Saturation, competition, and asymmetry. J Gen Physiol, 81, 221-237. McNaught, K. S., Carrupt, P. A., Altomare, C., Cellamare, S., Carotti, A., Testa, B., Jenner, P. and Marsden, C. D. (1998) Isoquinoline derivatives as endogenous neurotoxins in the aetiology of Parkinson's disease. Biochem Pharmacol, 56, 921-933. Meredith, G. E., Sonsalla, P. K. and Chesselet, M. F. (2008) Animal models of Parkinson's disease progression. Acta Neuropathol, 115, 385-398. Mravec, B. (2006) Salsolinol, a derivate of dopamine, is a possible modulator of catecholaminergic transmission: a review of recent developments. Physiol Res, 55, 353-364. Muller, T., Przuntek, H., Kuhn, W., Baum, S. S. and Rommelspacher, H. (1999) No increase of synthesis of (R)salsolinol in Parkinson's disease. Mov Disord, 14, 514-515. Musshoff, F., Schmidt, P., Dettmeyer, R., Priemer, F., Jachau, K. and Madea, B. (2000) Determination of dopamine and dopamine-derived (R)-/(S)-salsolinol and norsalsolinol in various human brain areas using solid-phase extraction and gas chromatography/mass spectrometry. Forensic Sci Int, 113, 359-366. Nagatsu, T. (1997) Isoquinoline neurotoxins in the brain and Parkinson's disease. Neurosci Res, 29, 99-111. Nagatsu, T. and Yoshida, M. (1988) An endogenous substance of the brain, tetrahydroisoquinoline, produces parkinsonism in primates with decreased dopamine, tyrosine hydroxylase and biopterin in the nigrostriatal regions. Neurosci Lett, 87, 178-182. Naoi, M., Maruyama, W., Matsubara, K. and Hashizume, Y. (1997) A neutral N-methyltransferase activity in the striatum determines the level of an endogenous MPP+-like neurotoxin, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, in the substantia nigra of human brains. Neurosci Lett, 235, 81-84. Naoi, M., Maruyama, W., Nakao, N., Ibi, T., Sahashi, K. and Benedetti, M. S. (1998) (R)salsolinol N-methyltransferase activity increases in parkinsonian lymphocytes. Annals of Neurology, 43, 212-216. Nie, W., Sweetser, S., Rinella, M. and Green, R. M. (2005) Transcriptional regulation of murine Slc22a1 (Oct1) by peroxisome proliferator agonist receptor-alpha and -gamma. Am J Physiol Gastrointest Liver Physiol, 288, G207-212. Niwa, T., Takeda, N., Kaneda, N., Hashizume, Y. and Nagatsu, T. (1987) Presence of tetrahydroisoquinoline and 2-methyl-tetrahydroquinoline in parkinsonian and normal human brains. Biochem Biophys Res Commun, 144, 1084-1089. Niwa, T., Takeda, N., Yoshizumi, H., Tatematsu, A., Yoshida, M., Dostert, P., Naoi, M. and Nagatsu, T. (1991) Presence of 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline and 1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, novel endogenous amines, in parkinsonian and normal human brains. Biochem Biophys Res Commun, 177, 603-609. Ohtsuki, S., Yamaguchi, H., Kang, Y. S., Hori, S. and Terasaki, T. (2010) Reduction of L-type amino acid transporter 1 mRNA expression in brain capillaries in a mouse model of Parkinson's disease. Biol Pharm Bull, 33, 1250-1252. Okura, T., Kato, S., Takano, Y., Sato, T., Yamashita, A., Morimoto, R., Ohtsuki, S., Terasaki, T. and Deguchi, Y. (2011) Functional characterization of rat plasma membrane monoamine transporter in the blood-brain and blood-cerebrospinal fluid barriers. J Pharm Sci, 100, 3924-3938. Pelis, R. M., Suhre, W. M. and Wright, S. H. (2006) Functional influence of N-glycosylation in OCT2-mediated tetraethylammonium transport. Am J Physiol Renal Physiol, 290, F1118-1126. Perry, V. H. (2004) The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease. Brain Behav Immun, 18, 407-413. Poller, B., Drewe, J., Krahenbuhl, S., Huwyler, J. and Gutmann, H. (2010) Regulation of BCRP (ABCG2) and P-glycoprotein (ABCB1) by cytokines in a model of the human blood-brain barrier. Cell Mol Neurobiol, 30, 63-70. Ransom, B. R., Kunis, D. M., Irwin, I. and Langston, J. W. (1987) Astrocytes convert the parkinsonism inducing neurotoxin, MPTP, to its active metabolite, MPP+. Neurosci Lett, 75, 323-328. Salkeni, M. A., Lynch, J. L., Otamis-Price, T. and Banks, W. A. (2009) Lipopolysaccharide impairs blood-brain barrier P-glycoprotein function in mice through prostaglandin- and nitric oxide-independent pathways. J Neuroimmune Pharmacol, 4, 276-282. Sandler, M., Carter, S. B., Hunter, K. R. and Stern, G. M. (1973) Tetrahydroisoquinoline alkaloids: in vivo metabolites of L-dopa in man. Nature, 241, 439-443. Shokunbi, M. T. and Gelb, A. W. (1990) Cortical-evoked potentials and cerebral infarction in temporary middle cerebral artery occlusion in the cat. Afr J Med Med Sci, 19, 213-218. Storch, A., Hwang, Y. I., Gearhart, D. A., Beach, J. W., Neafsey, E. J., Collins, M. A. and Schwarz, J. (2004) Dopamine transporter-mediated cytotoxicity of beta-carbolinium derivatives related to Parkinson's disease: relationship to transporter-dependent uptake. J Neurochem, 89, 685-694. Storch, A., Ott, S., Hwang, Y. I. et al. (2002) Selective dopaminergic neurotoxicity of isoquinoline derivatives related to Parkinson's disease: studies using heterologous expression systems of the dopamine transporter. Biochem Pharmacol, 63, 909-920. Suzuki, K., Kosho, I. and Namiki, H. (2008) Characterization of the unique regulatory mechanisms of phorbol ester-induced polymorphonuclear leukocyte spreading in an acidified environment. Eur J Pharmacol, 588, 301-308. Taubert, D., Grimberg, G., Stenzel, W. and Schomig, E. (2007) Identification of the endogenous key substrates of the human organic cation transporter OCT2 and their implication in function of dopaminergic neurons. PLoS One, 2, e385. Vee, M. L., Lecureur, V., Stieger, B. and Fardel, O. (2009) Regulation of drug transporter expression in human hepatocytes exposed to the proinflammatory cytokines tumor necrosis factor-alpha or interleukin-6. Drug Metab Dispos, 37, 685-693. von Wedel-Parlow, M., Wolte, P. and Galla, H. J. (2009) Regulation of major efflux transporters under inflammatory conditions at the blood-brain barrier in vitro. J Neurochem, 111, 111-118. Xia, L., Engel, K., Zhou, M. and Wang, J. (2007) Membrane localization and pH-dependent transport of a newly cloned organic cation transporter (PMAT) in kidney cells. Am J Physiol Renal Physiol, 292, F682-690. Yamakawa, T., Kotake, Y., Fujitani, M., Shintani, H., Makino, Y. and Ohta, S. (1999) Regional distribution of parkinsonism-preventing endogenous tetrahydroisoquinoline derivatives and an endogenous parkinsonism-preventing substance-synthesizing enzyme in monkey brain. Neurosci Lett, 276, 68-70. Yoshida, M., Niwa, T. and Nagatsu, T. (1990) Parkinsonism in monkeys produced by chronic administration of an endogenous substance of the brain, tetrahydroisoquinoline: the behavioral and biochemical changes. Neurosci Lett, 119, 109-113. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/63448 | - |
| dc.description.abstract | N-methyl-(R)salsolinol (N-methyl-(R)SAL) and 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1-benzyl-TIQ) are endogeneous neurotoxins that can induce parkinsonism in animals. The concentrations of N-methyl-(R)SAL and 1-benzyl-TIQ in CSF are 2-3 times higher in PD patients than in control subjects. The present study was to investigate whether N-methyl-(R)SAL and 1-benzyl-TIQ can be transported by human OCT2 (hOCT2) and human PMAT (hPMAT). Also, the effects of aging on the expression of these transporters were examined.
MDCKII-hOCT2 and MDCKII-hPMAT cell lines were established and the kinetic properties of N-methyl-(R)SAL and 1-benzyl-TIQ were measured. The expression of OCT2 and PMAT was measured in terms of aging and LPS treatment. Accordingly, quantitative polymerase chain reaction (qPCR) and Western blotting/immunofluorescence were used to measure mRNA and protein expression of OCT2 and PMAT, respectively. Also, the concentrations of cytokines and chemokine in the serum of aging mice were analyzed by cytometric bead array. The results showed that both 1-benzyl-TIQ and N-methyl-(R)SAL competitively inhibited MPP+ uptake in MDCKII-hOCT2 and MDCKII-hPMAT cells. 1-benzyl-TIQ was a substrate of hOCT2 (Km and Vm values of 13.5±3.7 μM and 3088.3±391.0 pmole/mg protein/min) and hPMAT (Km and Vm values of 184.0±49.9 μM and 8544.8±802.3 pmole/mg protein/min). Although N-methyl-(R)SAL can be transported by hOCT2 (Km and Vm values of 185.0±265.6 μM and 7857.9±5139.4 pmole/mg protein/min), N-methyl-(R)SAL was not a substrate of hPMAT. The values of transport efficiency (Vm/Km) suggested that 1-benzyl-TIQ was mainly transported by hOCT2 at low concentrations. OCT2 and PMAT mRNA levels were decreased in the brain of aging mice and their protein levels were also decreased in brain capillaries of aging mice. The concentrations of serum cytokines and chemokine were increased with aging indicating the association between aging and inflammation. However, OCT2 and PMAT proteins were increased in brain capillaries in mice after 24-hr LPS treatment. In conclusion, OCT2 is important for the transport of N-methyl-(R)SAL and 1-benzyl-TIQ. The down-regulation of OCT2 in brain capillaries of aging mice may result in the decrease of clearance in these neurotoxins. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T16:42:25Z (GMT). No. of bitstreams: 1 ntu-101-R99423016-1.pdf: 2116704 bytes, checksum: b3e4f511837081dbaa741a7dedbe40a4 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | Abstract …………................................................................................. i
中文摘要 ……………………………………………………………...... iii 目錄 ………………………………………………………………... v 圖目錄 ………………………………………………………………... viii 表目錄 ………………………………………………………………... x 縮寫對照表 ………………………………………………………………... xi 第一章 文獻回顧…...………………………………………………… 1 1.1 巴金森氏症 (Parkinson’s disease，PD)……………………… 1 1.2 神經毒性物質………………….………..........……………… 2 1.2.1 內生性tetrahydroisoquinoline類化合物在腦部的分布……. 3 1.3 TIQ與細胞膜轉運蛋白……................................................... 3 1.4 老化對於轉運蛋白的調控…………………………………... 6 第二章 研究目的…...………………………………………………… 16 第三章 實驗方法…...………………………………………………… 17 3.1 實驗材料……………...……………………………………… 17 3.2 實驗步驟…...………………………………………………… 23 3.2.1 hOCT2/hENT4基因轉殖.…………………………………… 23 3.2.2 細胞膜蛋白萃取…………………...………………………… 25 3.2.3 蛋白質濃度測定 (Bio-Rad DC protein assay)……………… 25 3.2.3.1 細胞溶解物 (Total cell lysate) 之蛋白濃度測定…………... 25 3.2.3.2 細胞膜蛋白萃取物與腦微血管蛋白萃取物之蛋白質濃度測定…………………………………………………………... 26 3.2.4 西方墨點法 (Western Blot)…………………………………. 26 3.2.5 MDCK-hOCT2/MDCK-hPMAT system之確認…………..... 27 3.2.5.1 時間相依性研究……………………………………………... 27 3.2.5.2 濃度相依性研究………………………………..................... 28 3.2.6 N-methyl-(R)SAL與1-benzyl-TIQ抑制3H-MPP+在MDCK- hOCT2與MDCK-hPMAT攝取量之研究………………….. 28 3.2.7 N-methyl-(R)SAL與1-benzyl-TIQ 在MDCK-hOCT2與MDCK- hPMAT之動力學研究……………………………... 29 3.2.7.1 時間相依性研究……………………………………………... 30 3.2.7.2 濃度相依性研究……………………………………………... 30 3.2.7.3 超高效液態層析串聯質譜儀 (UPLC-MS-MS) 定量分析… 31 3.2.8 反轉錄及定量聚合酶鏈鎖反應 (Reverse transcription- quantitative polymerase chain reaction, RT-qPCR) …….…… 31 3.2.8.1 反轉錄反應(RT; reverse transcription) …...…………………. 31 3.2.8.2 定量即時聚合酶鏈鎖反應 (real time-quantitative polymerase chain reaction)…………...……………………..... 32 3.2.9 分離小鼠腦部微血管……………...………………………… 32 3.2.10 流式細胞儀分析血清中細胞激素和趨化激素之濃度……... 34 3.2.10.1 IL-6, IL-10, MCP-1, IFN-γ, TNF, IL-12p70…….……..……. 34 3.2.10.2 IL-1α and IL-1β…….…….…….…….…………..…….……. 34 3.2.11 數據分析.…….…………..…….….…….…………..…….… 35 第四章 實驗結果.…….…………..…….….…….…………..…….… 39 4.1 MDCK-hOCT2及MDCK-hPMAT之建立.…….………….. 39 4.1.1 MDCK-hOCT2.…….…………..…….….…….…………..… 39 4.1.2 MDCK-hPMAT.…….…………..…….….…….…………..… 40 4.2 N-methyl-(R)SAL/1-benzyl-TIQ與MPP+在MDCK-hOCT2上作用關係之探討.…….…………..…….….…….………… 41 4.3 N-methyl-(R)SAL與1-benzyl-TIQ在MDCK-hOCT2 的動力學試驗.…….…………..…….….…….…………..…….…. 42 4.3.1 N-methyl-(R)SAL與1-benzyl-TIQ在MDCK-hOCT2的攝取量之時間相依性研究.…….…………..…….…………….. 42 4.3.2 N-methyl-(R)SAL與1-benzyl-TIQ在MDCK-hOCT2的攝取量之濃度相依性研究.…….…………..…….….…….…… 42 4.4 N-methyl-(R)SAL與1-benzyl-TIQ與MPP+在MDCK- hPMAT細胞上作用關係之探討.…….………….………..… 43 4.5 N-methyl-(R)SAL與1-benzyl-TIQ在MDCK-hPMAT的動力學試驗.…….…………..…….….…….…………..…….… 44 4.5.1 N-methyl-(R)SAL與1-benzyl-TIQ在MDCK-hPMAT的攝取量之時間相依性研究.…….…………..………………….. 44 4.5.2 N-methyl-(R)SAL與1-benzyl-TIQ在MDCK-hPMAT的攝取量之濃度相依性研究.…….…………..…….….…………. 45 4.6 老化對於腦部有機陽離子轉運蛋白表現量之影響…..……. 45 4.7 老化對於腦部微血管中有機陽離子轉運蛋白表現量之影響…..………..………..………..………..………..………….. 46 4.8 老化對於血清中細胞激素與趨化激素含量之影響…..……. 46 4.9 發炎對於腦部微血管中有機陽離子轉運蛋白之影響…..…. 47 第五章 結果討論…..………..………..………..………..………..….. 64 第六章 結論…..………..………..………..………..………..……….. 69 第七章 參考文獻……………………………………………………... 70 | |
| dc.language.iso | zh-TW | |
| dc.subject | 有機陽離子轉運蛋白 | zh_TW |
| dc.subject | 巴金森氏症 | zh_TW |
| dc.subject | PD | en |
| dc.subject | BBB | en |
| dc.subject | OCT | en |
| dc.subject | 1-benzyl-TIQ | en |
| dc.subject | N-methyl-(R)SAL | en |
| dc.title | 有機陽離子轉運蛋白OCT2/PMAT與N-methyl-(R)SAL/1-benzyl-TIQ作用關係以及老化對腦部OCT2/PMAT表現影響之研究 | zh_TW |
| dc.title | The interaction between OCT2/PMAT and N-methyl-(R)SAL/1-benzyl-TIQ, and the expression of OCT2/PMAT in the brain of senescent mice | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蔡亭芬,陳儀莊,劉宏輝,許麗卿 | |
| dc.subject.keyword | 有機陽離子轉運蛋白,巴金森氏症, | zh_TW |
| dc.subject.keyword | N-methyl-(R)SAL,1-benzyl-TIQ,OCT,BBB,PD, | en |
| dc.relation.page | 75 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-24 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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