神经药理学报››2011,Vol. 1››Issue (5): 49-55.
胡敏1,2,何治1,2
出版日期:
2011-10-26发布日期:
2013-03-24通讯作者:
何治,男,神经药理学博士,副教授,硕士研究生导师;研究方向:神经药理学;E-mail:hezhi2003@163.com作者简介:
胡敏,女,在读硕士研究生;E-mail:humin71325@163.com基金资助:
国家自然科学基金青年科学基金项目(No.81100873),湖北省卫生厅青年科技人才项目(No.QJX2012-27),宜昌市科学技术研究与开发项目(No.A01301-02)
HU Min1,2,HE Zhi1,2
Online:
2011-10-26Published:
2013-03-24Contact:
何治,男,神经药理学博士,副教授,硕士研究生导师;研究方向:神经药理学;E-mail:hezhi2003@163.comAbout author:
胡敏,女,在读硕士研究生;E-mail:humin71325@163.comSupported by:
国家自然科学基金青年科学基金项目(No.81100873),湖北省卫生厅青年科技人才项目(No.QJX2012-27),宜昌市科学技术研究与开发项目(No.A01301-02)
摘要:缺血性脑血管病是常见病、多发病,其致残率和死亡率均高,严重影响着人类的身体健康和生活质量。而脑缺血缺氧时,神经元会出现损伤和死亡。现有大量研究证明α2-肾上腺素受体激动剂能保护大脑神经元免受缺血/再灌注的损伤,但其发挥神经保护作用的确切机制尚不完全清楚,可能与α2-肾上腺素受体的激活有关。右旋美托嘧啶就是一种高选择性的α2-肾上腺素受体激动剂,具有一定的神经保护作用。本文就缺血性脑血管病病理生理演变过程、右旋美托嘧啶的分子药理学及其发挥神经保护作用的机制作一综述。
中图分类号:
胡敏, 何治. α2-肾上腺素受体激动剂右旋美托嘧啶对缺血性脑血管病的保护作用[J]. 神经药理学报, 2011, 1(5): 49-55.
HU Min, HE Zhi. Neuroprotective role of the Alpha 2-Adrenergic Agonist Dexmedetomidine in Ischemic Cerebrovascular Disease[J]. ACTA NEUROPHARMACOLOGICA, 2011, 1(5): 49-55.
1. Guo Min-fang, Yu Jie-zhong, Ma Cun-gen. Mechanisms related to neuron injury and death in cerebral hypoxic ischaemia[J]. Folia Neuropathol, 2011, 49(2): 78-87. 2. Kamibayashi Takahiko, Maze Mervyn. Clinical uses of α2-adrenergic agonists[J]. Anesthesiol, 2000, 93(5): 1345-1349. 3. Ilfeld Brian M, Morey Timothy E, Thannikary Lisa J, et al. Clonidine added to a continuous interscalene ropivacaine perineural infusion to improve postoperative analgesia: a randomized, double-blind, controlled study[J]. Anesth Analg, 2005, 100(4): 1172-1178. 4. Ma Daqing, Rajakumaraswamy Nishanthan, Maze Mervyn. α2-Adrenoceptor agonists: shedding light on neuroprotection?[J]. Br Med Bull, 2005, 71(1): 77-92. 5. Bell Marshall T, Puskas Ferenc, Smith Phillip D, et al. Attenuation of spinal cord ischemia-reperfusion injury by specific alpha-2a receptor activation with dexmedetomidine[J]. J Vasc Surg, 2012, 56(5): 1398-1402. 6. Uysal Hale Yarkan, Cuzdan Suat Sedat, Kayiran Oguz, et al. Preventive effect of dexmedetomidine in ischemia-reperfusion injury[J]. J Craniofac Surg, 2012, 23(5): 1287-1291. 7. Kilic Kemal, Hanci Volkan, Selek Sahbettin, et al. The effects of dexmedetomidine on mesenteric arterial occlusion-associated gut ischemia and reperfusion-induced gut and kidney injury in rabbits[J]. J Surg Res, 2012, 178(1): 223-232. 8. 刘学升. 缺血性脑血管病的病理生理[M]//邢成名. 缺血性脑血管病.第一版. 北京: 人民卫生出版社,2003: 110-153. 9. 任长和, 欧册华. 右美托咪啶脑保护作用的研究进展[J]. 医学综述, 2012, 18(5): 721-723. 10. 张挺, 李丽琴. α2肾上腺素受体的结构及其生物学功能[J]. 生命的化学, 2006, 26(3): 266-269. 11. Cotecchia Susanna, Kobilka Brain K, Daniel Kiefer W, et al. Multiple second messenger pathways of α-adrenergic receptor subtypes expressed in eukaryotic cells[J]. J Biol Chem, 1990, 265(1): 63-69. 12. Hayashi Yukio, Rabin Bradford C, Guo Tianzhi, et al. Role of pertussis toxin-sensitive G-proteins in the analgesic and anesthetic actions of α2-adrenergic agonists in the rat[J]. Anesthesiology, 1995, 83(4): 816-822. 13. 郭荣, 程芮. 右美托咪定对脑缺血性损伤的保护作用[J]. 中国新药与临床杂志, 2012, 31(4): 197-201. 14. Ostopovici-Halip Liliana, Curpan Ramona, Mracec Maria, et al. Structural determinants of the alpha2 adrenoceptor subtype selectivity[J]. J Mol Graph Model, 2011, 29(8): 1030-1038. 15. Casanovas Anna, Olmos Gabriel, Ribera Joan, et al. Induction of reactive astrocytosis and prevention of motoneuron cell death by the I2-imidazoline receptor ligand LSL 60101[J]. Br J Pharmacol, 2000, 130(8): 1767-1776. 16. 苏瑞斌, 李锦. 咪唑啉I2受体研究进展[J]. 中国药理学与毒理学杂志, 2004, 18(1): 75-78. 17. Broughton Brad R, Reutens David C, Sobey Christopher G. Apoptotic mechanisms after cerebral ischemia[J]. Stroke, 2009, 40(5): e331-e339. 18. Scanziani Massimo, Gahwiler Beat H, Thompson Scott M. Presynaptic inhibition of excitatory synaptic transmission mediated by α adrenergic receptors in area CA3 of the rat hippocampus in vitro[J]. J Neurosci, 1993, 13(12): 5393-5401. 19. Boehm Stefan. Presynaptic α2-adrenoceptors control excitatory, but not inhibitory, transmission at rat hippocampal synapses[J]. J Physiol, 1999, 519(2): 439-449. 20. Berkman M Zafer, Zirh T Ali, Berkman Kemal, et al. Tizanidine is an effective agent in the prevention of focal cerebral ischemia in rats: an experimental study[J]. Surg Neurol, 1998, 50(3): 264-270. 21. Jellish W Scott, Murdoch John, Kindel Gisela, et al. The effect of clonidine on cell survival, glutamate, and aspartate release in normo- and hyperglycemic rats after near complete forebrain ischemia[J]. Exp Brain Res, 2005, 167(4): 526-534. 22. Chiu Kuanming, Lin Tzuyu, Lu Chengwei, et al. Inhibitory effect of glutamate release from rat cerebrocortical nerve terminals by alpha2 adrenoceptor agonist dexmedetomidine[J]. Eur J Pharmacol, 2011, 670(1): 137-147. 23. Huang Rong, Chen Ye, Yu A C, et al. Dexmedetomidine-induced stimulation of glutamine oxidation in astrocytes: a possible mechanism for its neuroprotective activity[J]. J Cereb Blood Flow Metab, 2000, 20(6): 895-898. 24. Engelhard Kristin, Werner Christian, Kaspar Susanne, et al. Effect of the alpha2-agonist dexmedetomidine on cerebral neurotransmitter concentrations during cerebral ischemia in rats[J]. Anesthesiology, 2002, 96(2): 450-457. 25. Simonson Steven G, Zhang Jing, Canada Andrew T Jr, et al. Hydrogen peroxide production by monoamine oxidase during ischemia-reperfusion in the rat brain[J]. J Cereb Blood Flow Metab, 1993, 13(1): 125-134. 26. Langer S Z. Presynaptic regulation of the release of catecholamines[J]. Pharmacol Rev, 1980, 32(4): 337-362. 27. Kuhmonen Johanna, Pokorny Jaroslav, Miettinen Riitta, et al. Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after transient global ischemia[J]. Anesthesiology, 1997, 87(2): 371-377. 28. Nacif-Coelho Carla, Correa-Sales Christiane, Chang Louise Lenoir, et al. Perturbation of ion channel conductance alters the hypnotic response to the alpha 2-adrenergic agonist dexmedetomidine in the locus coeruleus of the rat[J]. Anesthesiology, 1994, 81(6): 1527-1534. 29. Gorini A, Villa Roberto Federico. Effect of in vivo treatment of clonidine on ATP-ase's enzyme systems of synaptic plasma membranes from rat cerebral cortex[J]. Neurochem Res, 2001, 26(7): 821-827. 30. Eser Olcay, Fidan Huseyin, Sahin Onder, et al. The influence of dexmedetomidine on ischemic rat hippocampus[J]. Brain Res, 2008, 1218: 250-256. 31. Engelhard Kristin, Werner Christian, Eberspacher Eva, et al. The effect of the alpha 2-agonist dexmedetomidine and the N-methyl-D-aspartate antagonist S(+)-ketamine on the expression of apoptosis-regulating proteins after incomplete cerebral ischemia and reperfusion in rats[J]. Anesth Analg, 2003, 96(2): 524-531. 32. Sanders R D, Sun P, Patel S, et al. Dexmedetomidine provides cortical neuroprotection: impact on anaesthetic-induced neuroapoptosis in the rat developing brain[J]. Acta Anaesthesiol Scand, 2010, 54(6): 710-716. 33. Dahmani Souhayl, Rouelle Danielle, Gressens Pierre, et al. Effects of dexmedetomidine on hippocampal focal adhesion kinase tyrosine phosphorylation in physiologic and ischemic conditions[J]. Anesthesiology, 2005, 103(5): 969-977. 34. 吕佩源, 胡亚卓, 肖向建, 等. 血管性痴呆小鼠海马ERK2及p-ERK的表达特征[J]. 神经疾病与精神卫生, 2007, 7(4): 251-253. 35. Dahmani Souhayl, Paris Andrea, Jannier Virginie, et al. Dexmedetomidine increases hippocampal phosphorylated extracellular signal-regulated protein kinase 1 and 2 content by an α2-adrenoceptor-independent mechanism: evidence for the involvement of imidazoline I1 receptors[J]. Anesthesiology, 2008, 108(3): 457-466. 36. Schoeler Marc, Loetscher Philip D, Rossaint Rolf, et al. Dexmedetomidine is neuroprotective in an in vitro model for traumatic brain injury[J]. BMC Neurol, 2012, 12(1): 20. 37. 韩新生, 吕建瑞, 张珍妮, 等. ERK抑制剂PD98059对SD大鼠全脑缺血再灌注后海马Caspase-3表达的影响[J]. 山西医科大学学报, 2012, 43(2): 81-84. 38. 路文婷, 陈朝旺, 高俊玲. 大鼠脑创伤后ERK信号转导通路对神经细胞凋亡的影响[J]. 中国医药导报, 2012, 9(18): 39-41. 39. 牛非, 胡金凤, 苑玉和, 等. 星形胶质细胞在脑缺血中的变化和作用[J]. 中国药理学通报, 2011, 27(10): 1342-1345. 40. Qu Yi, Duan Zhou-jin, Zhao Feng-yan, et al. Telomerase reverse transcriptase upregulation attenuates astrocyte proliferation and promotes neuronal survival in the hypoxic-ischemic rat brain[J]. Stroke, 2011, 42(12): 3542-3550. 41. 沙晶, 朱沂, 党辉, 等. 脑缺血/再灌注损伤对小鼠海马区胶质细胞的影响[J]. 新疆医科大学学报, 2012, 35(2): 158-162. 42. Zhao Z, Code W E, Hertz L. Dexmedetomidine, a potent and highly specific alpha 2 agonist, evokes cytosolic calcium surge in astrocytes but not in neurons[J]. Neuropharmacology, 1992, 31(10): 1077-1079. 43. Huang Rong, Hertz Leif. Clonidine enhances astrocytic glutamine uptake by authentic alpha 2-adrenoceptor stimulation[J]. Neuroreport, 1994, 5(5): 632-634. 44. Yan Min, Dai Hai-bin, Ding Ting-ting, et al. Effects of dexmedetomidine on the release of glial cell line-derived neurotrophic factor from rat astrocyte cells[J]. Neurochem Int, 2011, 58(5): 549-557. 45. Reis D J, Regunathan S, Golanov E V, et al. Protection of focal ischemic infarction by rilmenidine in the animal: evidence that interactions with central imidazoline receptors may be neuroprotective[J]. Am J Cardiol, 1994, 74(13): 25A-30A. |
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