神经药理学报 ›› 2016, Vol. 6 ›› Issue (6): 45-54.DOI: 10.3969/j.issn.2095-1396.2016.06. 005
徐唯哲，李晓蓉，熊杰，徐平湘，薛明
出版日期:2016-12-26
发布日期:2017-01-03
通讯作者:
国家自然科学基金项目（No.81573683），北京市自然科学基金暨市教委重点项目（No.KZ201110025024）
作者简介:徐唯哲，男，硕士；研究方向：药代动力学；Tel：+86-010-83950162，E-mail：xwzccmu@126.com
基金资助:国家自然科学基金项目（No.81573683），北京市自然科学基金暨市教委重点项目（No.KZ201110025024）
XU Wei-zhe，LI Xiao-rong，XIONG Jie，XU Ping-xiang，XUE Ming
Online:2016-12-26
Published:2017-01-03
Contact:
国家自然科学基金项目（No.81573683），北京市自然科学基金暨市教委重点项目（No.KZ201110025024）
About author:徐唯哲，男，硕士；研究方向：药代动力学；Tel：+86-010-83950162，E-mail：xwzccmu@126.com
Supported by:国家自然科学基金项目（No.81573683），北京市自然科学基金暨市教委重点项目（No.KZ201110025024）
摘要： 药物转运体（transporters）是指位于生物体细胞膜上的功能性转运蛋白，这些转运蛋白控制着生物体的内、外源性物质的流入和流出，以达到机体的物质稳态平衡。基于血脑屏障的膜转运蛋白在神经和精神药物的药动学、药效学及毒理学中均起着十分重要的作用，其既决定药物在血浆和脑组织中的浓度水平，也与治疗效应和毒副作用密切相关。本文综述了基于血脑屏障的神经药物转运体的研究概况。
徐唯哲，李晓蓉，熊杰，徐平湘，薛明. 基于血脑屏障的神经药物转运体研究概况[J]. 神经药理学报, 2016, 6(6): 45-54.
XU Wei-zhe，LI Xiao-rong，XIONG Jie，XU Ping-xiang，XUE Ming. An Overview of the Transporters for the Neurodrugs Based on the Blood-Brain Barrier[J]. Acta Neuropharmacologica, 2016, 6(6): 45-54.
| [1] P Borst, R Oude Elferink. Mammalian ABC transporters in health and disease [J]. Ann Rev Biochem, 2003, 71(1):537-592.[2] Matthias A Hediger, Michael F Romero, Peng Ji-bin, et al. The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins [J]. Pflügers Archiv Eur J Physiol, 2003, 447(5):465-8.[3] Coen C Paulusma, Piter J Bosma, Guido J R Zaman, et al. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene [J]. Science, 1996, 271:1126-1128.[4] Jonathon Burman, Cindy H Tran, Charles Glatt, et al. The effect of rare human sequence variants on the function of vesicular monoamine transporter [J]. Pharmacogenetics, 2004, 14:587-594.[5] Elaine M Leslie, Roger G Deeley, Susan P C Cole. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2 and BCRP in tissue defense [J]. Toxicol Appl Pharmacol, 2005, 204(3): 216-237.[6] Sun Hai-ying, Dai Hai-qing, Naveed Shaik, et al. Drug efflux transporters in the CNS [J]. Adv Drug Deliv Rev, 2003, 55(1): 83-105.[7] David J Begley, Milton W Brightman. Structural and functional aspects of the blood–brain barrier [J]. Prog Drug Res, 2003, 61:39-78.[8] James F List, Vincent Woo, Enrique Morales, et al. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes [J]. Diabetes Care, 2009, 32(4): 650-657.[9] 张健, 刘克辛. 药物转运体介导的小肠吸收、肾脏排泄与药物相互作用的关系 [J]. 药学学报, 2010(9):1089-1094. [10] Anupa K Patel, Vivian Fonseca. Turning glucosuria into a therapy: Efficacy and safety with SGLT2 inhibitors [J]. Curr Diabetes Rep, 2010, 10(2):101-107.[11] Hitesh Vaidya, Ramesh K Goyal. Exploring newer target sodium glucose transporter 2 for the treatment of diabetes mellitus [J]. Mini Rev Med Chem, 2010, 10(10):905-913.[12] Edward Chao, Robert R Henry. SGLT2 inhibition-a novel strategy for diabetes treatment [J]. Nature Rev Drug Discov, 2010, 9(7):551-559. [13] Robinson Sabino Silva, Rosana Mori, Aline David, et al. The Na+/glucose cotransporters: from genes to therapy [J]. Brazil J Med Biol Res, 2010, 43(11):1019-1026.[14] Wei Meng, Bruce A Ellsworth, Alexandra A Nirschl, et al. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes [J]. J Neurosci, 2008, 51(5):14271–14286.[15] Maria Florencia Albertoni Borghese. Monica Majowicz Albertoni. Inhibitors of sodium/glucose cotransport [J]. Drugs Future, 2009, 34(4):297-305.[16] 何聿娴, 刘晓东, 王新廷, 等. 钠依赖性葡萄糖转运体介导红景天苷在大鼠肠中吸收[J]. Chin J Nat Med, 2009(6): 444-448.[17] I Stuart Wood, Paul Trayhurn. Glucose transporters (GLUT and SGLT): expanded families of sugar transport proteins [J]. Brit J Nutr, 2003, 89(1):3-9.[18] Hans-Georg Joost, Bernard Thorens. The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members [J]. Mol Membr Biol, 2001, 18(4):247-256.[19] Hans-Georg Joost, Graeme I Bell, James D Best, et al. Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators [J]. Am J Endocrinol Metab, 2002, 282(4):E974-6.[20] Aramati B M Reddy, Satish K Srivastava, Kota V Ramana. Aldose reductase inhibition prevents lipopolysaccharide-induced glucose uptake and glucose transporter 3 expression in RAW264.7 macrophages [J]. Int J Biochem Cell Biol, 2010, 42(6):1039-1045.[21] Ala Jo, Park Jongmin, Seung Bum Park. Exploiting the mechanism of cellular glucose uptake to develop an image-based high-throughput screening system in living cells [J]. Chem Commun, 2013, 49(45):5138-5140.[22] Hyang Yeon Lee, Jae Jeong Lee, Jongmin Park, et al. Development of fluorescent glucose bioprobes and their application on real-time and quantitative monitoring of glucose uptake in living cells [J]. Chem, 2011, 17(1):143-150.[23] Roger G O’Neil, Ling Wu, Nizar Mullani. Uptake of a fluorescent deoxyglucose analog (2-NBDG) in tumor cells [J]. Mol Imag Biol, 2005, 7(7):388-92.[24] Oran Kwon, Peter Eck, Chen Sheng-lin, et al. Inhibition of the intestinal glucose transporter GLUT2 by flavonoids [J]. Faseb, 2007, 21(2):366-377.[25] Nakata M, Nagasaka S, Kusaka I, et al. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control [J]. Diabetologia, 2006, 49(8):1881-1892.[26] Takaguri A, Satoh K M, Tokumitsu Y, et al. Effects of atorvastatin and pravastatin on signal transduction related to glucose uptake in 3T3L1 adipocytes [J]. J Pharmacol Sci, 2008, 107(1):80-89.[27] Abraham J Al-Alahmad. Comparative study on glucose transporters expression and activity between stem cell-derived brain microvascular endothelial cells and hCMEC/D3 cells [J]. Am J Physiol Cell Physiol, 2017, doi: 10.1152/ajpcell.00116.2017.[28] Susanna Bodoy, Lorena Martin, Antonio Zorzano, et al. Identification of LAT4, a novel amino acid transporter with system L activity [J]. J Biol Chem, 2005, 280:12002-12011.[29] Andreas Reichel, N Joan Abbott, David J Begley. Evaluation of the RBE4 cell line to explore carrier-mediated drug delivery to the CNS via the L-system amino acid transporter at the blood-brain barrier [J]. J Drug Target, 2002, 10(4):277-283.[30] Segawa H, Fukasawa Y, Miyamoto K, et al. Identification and functional characterization of a Na+-independent neutral amino acid transporter with broad substrate selectivity [J]. J Biol Chem, 1999, 274(28):19745-19751.[31] Jarkko Rautio, Krista Laine, Mikko Gynther, et al. Prodrug approaches for CNS delivery [J]. Aaps J, 2008, 10(1):92-102.[32] Hiroshi Uchino, Yoshikatsu Kanai, Do Kyung Kim, et al. Transport of amino acid-related compounds mediated by L-type amino acid transporter 1 (LAT1): insights into the mechanisms of substrate recognition [J]. Mol Pharmacol, 2002, 61(4):729-737.[33] David Dickens, Steven Douglas Webb, Svetlana Antonyuk , et al. Transport of gabapentin by LAT1 (SLC7A5)[J]. Biochem Pharmacol, 2013, 85(11):1672-1683.[34] David A Groneberg, Frank Doring, Paul Eynott, et al. Intestinal peptide transport: ex vivo uptake studies and localization of peptide carrier PEPT1 [J]. Int J Comput Math, 2001, 281(3): 697-704.[35] Guillaume Dalmasso, Hang Thi Thu Nguyen, Laetitia Charrier-Hisamuddin, et al. PepT1 mediates transport of the proinflammatory bacterial tripeptide L-Ala-{gamma-D-Glu-meso-DAP in intestinal epithelial cells [J]. Am J Physiol-Gastro, 2010, 299(3): G687.[36] Guillaume Dalmasso, Hang Thi Thu Nguyen, Sarah A Ingersoll, et al. The PepT1-NOD2 signaling pathway aggravates induced colitis in mice [J]. J Gastroenterol, 2011, 141(4):1334-1345.[37] Tai Wan-yi, Chen Zhi-jin, Cheng Kun. Expression profile and functional activity of peptide transporters in prostate cancer cells [J]. Mol Pharm, 2012, 10(2):477-487.[38] Matthias Brandsch. Drug transport via the intestinal peptide transporter PepT1 [J]. Curr Opinion Pharmacol, 2013, 13(6):881-887.[39] Constanze Hilgendorf, Gustav Ahlin, Annick Seithel, et al. Expression of thirty-six drug transporter genes in human intestine, liver, kidney, and organotypic cell lines [J]. Drug Metab Dispo, 2007, 35(35):1333-40.[40] Andrew Bahn, Dirk Prawitt, Diana Buttler, et al. Genomic structure and in vivo expression of the human organic anion transporter 1 (hoat1) gene [J]. Biochem Biophy Res Commun, 2000, 275(2):623-30.[41] Eve-Irene Lepist, Zhang Xue-xiang, Hao Jia, et al. Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicista t[J]. Eur J Immunol, 2014, 36(11):2928-2938.[42] Shen Hong, Liu Tong-tong, Bridget L Morse, et al. Characterization of organic anion transporter 2 (slc22a7): a highly efficient transporter for creatinine and species-dependent renal tubular expression [J]. Drug Metab Dispos, 2015, 37(6):603-613.[43] Gerhard Burckhardt. Drug transport by organic anion transporters [J]. Pharmacol Thera, 2012, 136(1):106-30.[44] Zhang Lei, Mark J Dresser, Andrew T Gray, et al. Cloning and functional expression of a human liver organic cation transporter [J]. Brain Stimul, 2015, 8(2):913-921.[45] Johan W Jonker, Alfred H Schinkel. Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3) [J]. J Pharmacol Exp Thera, 2004, 308(1):2-9.[46] Wang L, Athina Giannoudis, Lane S, et al. Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia [J]. Clin Pharmacol Thera, 2008, 83(2):258-264.[47] Hermann Koepsell, Hitoshi Endou. The SLC22 drug transporter family [J]. EurJ Physiol, 2004, 447(5):666-76.[48] David L Bourdet, John B Pritchard, Dhiren R Thakker. Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 [J]. J Pharmacol Exp Thera, 2006, 315(3):1288-97.[49] Supratim Choudhuri, Curtis D Klaassen. Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters [J]. Int J Toxicol, 2006, 25(4):231-259.[50] Robert Ernst, Petra Kueppers, Jan Stindt, et al. Multidrug efflux pumps: Substrate selection in ATP-binding cassette multidrug efflux pumps-first come, first served [J]. Febs J, 2010, 277: 540-549.[51] Manthena V S Varma, Yasvanth Ashokraj, Chinmoy S Dey. P-glycoprotein inhibitors and their screening: a perspective from bioavailability enhancement [J]. J Ital Pharmacol Soc, 2003, 48(4):347-359.[52] Elaine M Leslie, Roger Deeley, Susan Cole. Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2 and BCRP (ABCG2) in tissue defense [J]. Toxicol Appl Pharmacol, 2005, 204: 216-237.[53] Kyoung-Ah Kim, Pil-Whan Park, Ji-Young Park. Effect of ABCB1 ( MDR1 ) haplotypes derived from G2677T/C3435T on the pharmacokinetics of amlodipine in healthy subjects [J]. Br J Clin Pharmacol, 2007, 63(1):53-58.[54] Christiane Pauli-Magnus, Deanna Kroetz. Functional implications of genetic polymorphisms in the multidrug resistance gene MDR1 (ABCB1) [J]. Pharm Res, 2004, 21(6):904-913.[55] Teodori E, Dei S, Martelli C, et al. The functions and structure of ABC transporters: implications for the design of new inhibitors of P-gp and MRP1 to control multidrug resistance (MDR) [J]. Curr Drug Targets, 2006, 15(2):167-176.[56] Marilyn E Morris, Vivian Rodriguez-Cruz, Melanie A Felmlee. SLC and ABC transporters: expression, localization, and species differences at the blood-brain and the blood-cerebrospinal fluid barriers [J]. AAPS J, 2017, doi: 10.1208/s12248-017-0110-8.[57] Clemens Braun, Atsushi Sakamoto, Holger Fuchs, et al. Quantification of transporter and receptor proteins in dog brain capillaries and choroid plexus: relevance for the distribution in brain and CSF of selected BCRP and P-gp substrates [J]. Mol Pharm, 2017, doi: 10.1021/acs.molpharmaceut. 7b00449.[58] Mahringer A, Fricker G. ABC transporters at the blood-brain barrier [J]. Expert Opin Drug Metab Toxicol, 2016, 12(5):499-508. [59] Nathalie Strazielle, Jean-Francois Ghersi-Egea. Efflux transporters in blood-brain interfaces of the developing brain [J]. Front Neurosci, 2015, 9:21-29. [60] Cole S P, Bhardwaj G, Gerlach J H, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line [J]. Science, 1992, 258(5088):1650-1654.[61] Andrew J Slot, Steven V Molinski, Susan P C Cole S. Mammalian multidrug-resistance proteins (MRPs) [J]. Essays Biochem, 2011, 50(1):179-207.[62] Shannon Dallas, David S Miller, Reina Bendayan. Multidrug resistance-associated proteins: expression and function in the central nervous system [J]. Pharmacol Rev, 2006, 58(2):140-161.[63] Shen S, Zhang W. ABC transporters and drug efflux at the blood-brain barrier [J]. Rev Neurosci, 2010, 21(1):29-53.[64] S M He, Li R, Jagat R Kanwar, et al. Structural and functional properties of human multidrug resistance protein 1 (MRP1/ABCC1) [J]. Curr Med Chem, 2011, 18(3):439-481.[65] Douglas D Ross, Takeo Nakanishi. Impact of breast cancer resistance protein on cancer treatment outcomes [J]. Meth Mol Biol, 2010, 596:251-290.[67] Kenji Oda, Tomohiro Nishimura, Kei Higuchi, et al. Estrogen receptor α induction by mitoxantrone increases Abcg2 expression in placental trophoblast cells [J]. J Pharm Sci, 2013, 102(9): 3364-3372.[68] Marilyn L Clarke, John R Mackey, Stephen A Baldwin, et al. The role of membrane transporters in cellular resistance to anticancer nucleoside drugs [J]. Cancer Treat Res, 2002, 112:27-47.[69] Gerd A Kullak-Ublick, Bruno Stieger, Peter J Meier. Enterohepatic bile salt transporters in normal physiology and liver disease [J]. Gastroenterol, 2004, 126(1): 322-342.[70] Mukta Agrawal, Ajazuddin, Dula K Tripathi, et al, Recent advancements in liposomes targeting strategies to cross blood-brain barrier for the treatment of Alzheimer's disease [J]. J Control Release, 2017, 260: 61-77.[71] Mitchell P McInerney, Jennifer L Short, Joseph A Nicolazzo. Neurovascular alterations in Alzheimer's disease: transporter expression profiles and cns drug access [J]. AAPS J, 2017, 19(4):940-956.[72] Satoki Imai, Ryota Kikuchi, Hiroyuki Kusuhara, et al. Analysis of DNA methylation and histone modification profiles of liver-specific transporters [J]. Mol Pharmacol, 2009, 75(3): 568-576.[73]Ciarimboli G. Organic cation transporters [J]. Xenbiotica, 2008, 38:936-971.[74] Benjamin J Andreone, Brian Wai Chow, Aleksandra Tata, et al. Blood-brain barrier permeability is regulated by lipid transport-dependent suppression of caveolae-mediated transcytosis [J]. Neuron, 2017, 94(3):581-594.[75] William M Pardridge. Blood-brain barrier endogenous transporters as therapeutic targets: a new model for small molecule CNS drug discovery [J]. Expert Opin Ther Targets, 2015, 19(8):1059-1072. [76] Atsushi Ose, Mototsugu Ito, Hiroyuki Kusuhara, et al. Limited brain distribution of Ro 64-0802 a pharmacologically active form of oseltamivir, by active efflux across the blood-brain barrier mediated by organic anion transporter 3 (OAT3/SLC22A8) and multidrug resistance-associated protein 4 (MRP4/ABCC4) [J]. Drug Metab Dispos, 2009, 37:315-321.[77] Akanuma S I, Shimada H, Kubo Y, et al. Involvement of carrier-mediated transport at the blood-cerebrospinal fluid barrier in spermine clearance from rat brain [J]. Biol Pharm Bull, 2017, 40(9):1599-1603. [78] Joseph W Polli, Katie L Olson, John P Chism, et al. An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the CNS penetration of the tyrosine kinase inhibitor lapatinib [J]. Drug Metab Dispos, 2009, 37:439-442.[79] Ryota Kikuchi, Hiroyuki Kusuhara, Takaaki Abe, et al. Involvement of multiple transporters in the efflux of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors across the blood-brain barrier [J]. J Pharmacol ExpTher, 2004, 311:1147-1153. [80] Agrawal M, Ajazuddin, Tripathi D K, et al. Recent advancements in liposomes targeting strategies to cross blood-brain barrier for the treatment of Alzheimer's disease [J]. J Control Release, 2017, 260:61-77.[81] Sotnikova T D, Beaulieu J M, Gainetdinov R R, et al. Molecular biology, pharmacology and functional role of the plasma membrane dopamine transporter [J]. CNS Neurol Disord Drug Targets, 2006, 5:45-56.[82] 张海威，张力. 血脑脊液屏障上P- 糖蛋白的研究进展[J].神经药理学报, 2016, 6（2）：53-64.[83] Anika M S Hartz, David S Miller, Bjorn Bauer. Restoring blood-brain barrier P-glycoprotein reduces brain amyloid beta in a mouse model of Alzheimer’s disease [J]. Mol Pharmacol, 2010, 77(5):715-723.[84] I Alexandru Bobulescu, Francesca Di Sole, Orson W Moe. Na+/H+ exchangers: physiology and link to hypertension and organ ischemia [J]. Mol Cell Biol Physiol, 2005, 14:485-494.[85] Gonzalo E Torres, Susan G Amara. Glutamate and monoamine transporters: New visions of form and function [J]. Curr Opin Neurobiol, 2007, 17(3):304-312.[86] Srividya Kidambi, Shailendra B Patel. Cholesterol and non-cholesterol sterol transporters: ABCG5, ABCG8 and NPC1L1: A review [J]. Xenobiotica, 2008, 38:1119-1139.[87] Brzica H, Abdullahi W, Ibbotson K, et al. Role of transporters in central nervous system drug delivery and blood-brain barrier protection: relevance to treatment of stroke [J]. J Cent Nerv Syst Dis, 2017, 9:117-129. [88] Naomi Mizuno, Takuro Niwa, Yoshihisa Yotsumoto, et al. Impact of drug transporter studies on drug discovery and development [J]. Pharmacol Rev, 2003, 55(3):425-461.[89]Marlyn Laksitorini, Vivitri D Prasasty, Paul K Kiptoo, et al. Pathway and progress in improving drug delivery through the intestinal mucosa and blood-brain barriers [J]. Ther Deliv, 2014, 5(10):1143-1163. [90] Reiner F Haseloff, Sophie Dithmer, Lars Winkler, et al. Transmembrane proteins of the tight junctions at the blood-brain barrier: structural and functional aspects [J]. Semin Cell Dev Biol, 2015, 38:16-25.[91] Abu J M Sadeque, Christoph Wandel, Hauibing He. Increased drug delivery to the brain by P-glycoprotein inhibition [J]. Clin Pharmacol Ther, 2000, 68:231-237.[92] Borst P, Elferink R O. Mammalian ABC transporters in health and disease [J]. Annu Rev Biochem, 2002, 71:537-592.[93] Gergely Szakacs, Jill Paterson, Joseph Ludwig, et al. Targeting multidrug resistance in cancer [J]. Nature Rev, 2006, 5: 219-234. [94] Nicola Antonio Colabufo, Francesco Berardi, Mariangela Cantore. Perspectives of P-glycoprotein modulating agents in oncology and neurodegenerative diseases: pharmaceutical, biological and diagnostic potentials [J]. J Med Chem, 2010, 53(5):1883-1897. [95] Li Xue, Hu Jin-Ping, Wang Bao-Lian. Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: herb drug interactions mediated via P-gp [J]. Toxicol Appl Pharm, 2014, 275(2): 163-175.[96] Nandhitha Subramanian, Karmen Condic-Jurkic, Megan L O'Mara. Structural and dynamic perspectives on the promiscuous transport activity of P-glycoprotein [J]. Neurochem Int, 2016, 98(10):146-152.[97] Xia Yuan-zheng, Ni Kai, Guo Chao, et al. Alopecurone B reverses doxorubicin-resistant human osteosarcoma cell line by inhibiting P-glycoprotein and NF-κB signaling [J]. Phytomedicine, 2015, 22(3):344-351.[98] Yang Xiao-fan, Ding Yu-feng, Xiao Miao, et al. Anti-tumor compound RY10-4 suppresses multidrug resistance in MCF-7/ADR cells by inhibiting PI3K/Akt/NF-κB signaling[J]. Chem Biol Interact, 2017, 278:22-31.[99] Toyoda Y, Hagiya Y, Adachi T, et al. MRP class of human ATP binding cassette (ABC) transporters: Historical background and new research directions [J]. Xenobiotica, 2008, 38(7-8): 833-862. |
| [1] | 杨靖，苑文英. 弓形虫感染对神经组织损伤及通过血脑屏障机制[J]. 神经药理学报, 2019, 9(5): 40-43. |
| [2] | 王静，程肖蕊，周文霞，张永祥. 快速老化模型小鼠海马囊泡谷氨酸转运体表达与兴奋性毒性关系的研究[J]. 神经药理学报, 2018, 8(2): 53-53. |
| [3] | 陈建，侯宏卫，刘勇，王安，胡清源. 血脑脊液屏障转运体研究方法的进展[J]. 神经药理学报, 2016, 6(3): 44-55. |
| [4] | 秦雪晴，杨志宏，孙晓波. 血脑屏障体外模型的研究进展[J]. 神经药理学报, 2016, 6(1): 25-34. |
| [5] | 陈方, 胡朦, 杜贯涛,刘广军, 洪浩. 2型糖尿病认知障碍发生机制研究进展[J]. 神经药理学报, 2013, 3(3): 27-33. |
| [6] | 黄继云，韩峰. 硝化应激参与介导缺血性脑损伤的研究进展[J]. 神经药理学报, 2011, 1(5): 56-64. |
| [7] | 薛占霞, 彭亮. 高血氨诱导肝性脑病发生发展的研究现状[J]. 神经药理学报, 2011, 1(4): 33-41. |
| 阅读次数 | ||||||
|
全文 |
|
|||||
|
摘要 |
|
|||||
