表明,自 由基及其内源性清除酶系统参与了低氧预适应的形成和发展。 2.7 其他机制 预适应可以降低细胞能量代谢。有实验表明,抑制线粒体复合物Ⅰ、Ⅱ可以形成预 适应,并可试用于提高机体的缺氧耐受能力[18]。低氧预适应引起的神经保护作用 可以被放线菌酮(一种蛋白合成抑制剂)和放线菌素D(一种RNA合成抑制剂)所抑制, 表明在低氧预适应中有新的基因表达产物形成[19]。热休克蛋白(HSP)是应激反应 蛋白家族中的一员,Wada等[20]用高温(41℃)预处理15 min和低氧(8%)预处理新生 大鼠3 h,24 h后予缺血处理,发现高温和低氧预处理后都不检测到HSP72,只是缺 氧缺血损害本身可诱导背侧纹状体、丘脑(轻度)和海马HSP72的表达,因此认为HS P72似与耐受无关。Garnier等[17]也发现,沙土鼠低氧预处理后海马未见HSP72表 达。星形细胞则参与细胞间液中K+代谢的调节和利用,维持神经元生存微环境的稳 定,分泌神经营养因子,如神经生长因子,从而参与了预适应保护机制。Garnier 等[17]用免疫组化和免疫印迹法检测胶质纤维酸性蛋白,并用免疫组化检测isole ctin B4的表达,结果表明沙土鼠低氧处理与小胶质细胞激活无关,而星形细胞却 明显被激活。 3 脑低氧预适应的应用前景 虽然脑低氧预适应的机制尚不十分清楚,但是预适应的效应提示脑组织具有自身保 护机制。如能对脑低氧预适应过程中产生的某些物质进行分离、纯化,试用于卒中 和其他缺血缺氧性疾病的治疗中,也许将提高脑神经元等组织对缺血缺氧的耐受性 ,延长治疗时间窗,减轻后遗症,并为脑损伤等疾病的防治提供新的选择。 参 考 文 献 1 Webster KA, Discher DJ, Bishopric NH. Cardioprotection in an in vitro model of hypoxic preconditioning. J Mol Cell Cardiol, 1995, 27(1): 453 -458. 2 Heurteaux C, Lauritzen I, Widmann C, et al. Essential role of adenosi ne, adenosine A1 receptors, and ATP-sensitive K+ channels in cerebral i schemic preconditioning. Proc Natl Acad Sci USA, 1995, 92(10): 4666-467 0. 3 Schurr A, Reid KH, Tseng MT, et al. Adaptation of adult brain tissue to anoxia and hypoxia in vitro. Brain Res, 1986, 374(2): 244-248. 4 Rising CL, D’Alecy LG. Hypoxia-induced increases in hypoxic toleranc e augmented by β-hydroxybutyrate in mice. Stroke, 1989, 20(9): 1219-122 5. 5 Vannucci RC, Towfighi J, Vannucci SJ. Hypoxic preconditioning and hyp oxic-ischemic brain damage in the immature rat: pathologic and metaboli c correlates. J Neurochem, 1998, 71(3): 1215-1220. 6 Bergeron M, Gidday J M, Yu AY, et al. Role of hypoxia-inducible facto r-1 in hypoxia-induced ischemic tolerance in neonatal rat brain. Ann Ne urol, 2000, 48(3): 285-296. 7 Ruscher K, Isaev N, Trendelenburg G, et al. Induction of hypoxia indu cible factor 1 by oxygen glucose deprivation is attenuated by hypoxic p reconditioning in rat cultured neurons. Neurosci Lett, 1998, 254(2): 11 7-120. 8 Gidday JM, Shah AR, Maceren RG, et al. Nitric oxide mediates cerebr al ischemic tolerance in a neonatal rat model of hypoxic precondition ing. J Cereb Blood Flow Metab, 1999, 19(3): 331-340. 9 Perez Pinzon MA, Mumford PL, Rosenthal M, et al. Anoxic preconditioni ng in hippocampal slices: role of adenosine. Neuroscience, 1996, 75(3): 687-694. 10 Zhang WL, Lu GW. Changes of adenosine and its A(1) receptor in hypox ic preconditioning. Biol Signals Recept, 1999, 8(4-5): 275-280. 11 Nakata N, Kato H, Kogure K. Ischemic tolerance and extracellular a mino acid concentrations in gerbil hippocampus measured by intracereb ral microdialysis. Brain Res Bul, 1994, 35(3): 247-251. 12 Xie J, Lu G, Hou Y. Role of excitatory amino acids in hypoxic precon ditioning. Biol Signals Recept, 1999, 8(4-5): 267-274. 13 Liu J, Ginis I, Spatz M, et al. Hypoxic preconditioning protects cul tured neurons against hypoxic stress via TNF-α and ceramide. Am J Phys iol Cell Physiol, 2000, 278(1): C144-C153. 14 Chen Y, Ginis I, Hallenbeck JM. The protective effect of ceramide in immature rat brain hypoxia-ischemia involves up-regulation of bcl-2 an d reduction of TUNEL-positive cells. J Cereb Blood Flow Metab, 2001, 21 (1): 34-40. 15 Duan C, Yan F, Song X, et al. Changes of superoxide dismutase, gluta thione perioxidase and lipid peroxides in the brain of mice preconditio ned by hypoxia. Biol Signals Recept, 1999, 8(4-5): 256-260. 16 Rauca C, Zerbe R, Jantze H, et al. The importance of free hydroxyl r adicals to hypoxia preconditioning. Brain Res, 2000, 868(1): 147-149. 17 Garnier P, Demougeot C, Bertrand N, et al. Stress response to hypoxi a in gerbil brain: HO-1 and MnSOD expression and glial activation. Brai n Res, 2001, 893(1-2): 301-309. 18 Riepe MW, Ludolph AC. Chemical preconditioning: a cytoprotective str ategy. Mol Cell Biochem, 1997, (1-2): 249-54. 19 Gage AT, Stanton PK. Hypoxia triggers neuroprotective alterations in hippocampal gene expression via a heme-containing sensor. Brain Res, 1 996, 719(1-2): 172-178. 20 Wada T, Kondoh T, Tamaki N. Ischemic “cross” tolerance in hypoxic ischemia of immature rat brain. Brain Res, 1999, 847(2): 299-307. 相关性
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