HIF1α在脑损伤中的作用及其机制的研究进展(3)

　　总之，HIF?1α在脑缺氧缺血性损伤中的保护机制研究尚未深入，很多方面仍未得到直接证据，而目前还存在争议。如Cramer等[29]在体外试验中发现在HIF?1α基因缺失的髓细胞，无论在缺氧环境还是正常氧浓度下，其ATP和乳酸的含量均明显降低，而乳酸含量是髓细胞活化发挥炎症作用的标志之一，提示HIF?1α可能会促进炎症反应的发生。另外，Helton等[30]通过敲除大鼠大脑HIF?1α基因发现，非但未增加缺氧缺血损伤，反而减轻了缺氧缺血后脑损伤。关于HIF?1α具体的脑保护作用机制仍有待进一步的研究和探讨。
　　4 问题与展望
　　HIF?1α对脑缺氧缺血性损伤的保护作用是多方面的，随着对HIF?1α及其下游缺氧反应基因研究的深入，其在脑缺氧缺血损伤中的作用会更加明确。HIF?1α有可能成为脑保护治疗中最有前途的靶基因，具有广阔的应用前景，它为临床治疗脑缺氧缺血性损伤提供了一种新的治疗策略。

【参考文献】
  　[1] Semenza GL, Wang GL.A nuclear factor induced by hypoxia via denovo protein synthesis binds to the human erythropoietin gene enhancer at site required for transcriptional activation[J].Mol Cell Biol, 1992, 12:5447?5454.

　　[2] Forsythe JA, Jiang BH, Iyer NV,et al.Activation of vascular endothelial growth factor gene transcription by hypoxia?inducible factor1[J].Mol Cell Biol, 1996, 16: 4604?4613.

　　[3] Wang GL, Jiang BH, Rue EA,et al.Hypoxia?inducible factor 1 is a basic?helix?loop?helix?PAS heterodimer regulated by cellular O2 tension[J].Proc Natl Acad Sci U S A, 1995, 92: 5510?5514.

　　[4] Wang GL, Semenza GL.Purification and characterization of hypoxia?inducible factor 1[J].J Biol Chem, 1995, 92: 1230?1237.

　　[5] Wenger RH. Cellular adaptation to hypoxia: O2?sensing protein hydroxylases, hypoxia?inducible transcription factors, and O2?regulated gene expression[J].FASEB J, 2002, 16: 1151?1162.

　　[6] Lee DW, Andersen JK. Role of HIF?1 in iron regulation: potential therapeutic strategy for neurodegenerative disorders[J].Curr Mol Med, 2006, 6(8): 883?893.

　　[7] Zhu Y, Lawton MT, Du R,et al.Expression of hypoxia?inducible factor?1 and vascular endothelial growth factor in response to venous hypertension[J].Neurosurgery, 2006, 59(3): 687?696.

　　[8] Calvert JW, Cahill J, Yamaguchi?Okada M,et al.Oxygen treatment after experiment hypoxia?ischemia in neonatal rats alters the expression of HIF?1 alpha and its downstream target genes[J].J Appl Physiol, 2006, 101(3): 853?865.

　　[9] Wang DP, Li HG, Li YJ,et al.Hypoxia?inducible factor l alpha cDNA cloning and its mRNA and protein tissue specific expression in domestic yak(Bos grunniens) from Qinghai?Tibetan platean[J].Biochem Biophys Res Commun, 2006, 348(1): 310?319.

　　[10] Bemaudin M, Nedelec AS, Divoux D,et al.Normobaric hypoxia induces tolerance to focal permanent cerebral ischemia in association with an increased expression of hypoxia?inducible factor?1 and its target genes, erythropoietin and VEGF, in the adult mouse brain[J].J Cereb Blood Flow Metab, 2002, 22(4): 393?403.

　　[11] Jones NM, Lee EM, Brown TG,et al.Hypoxic preconditioning produces differential expression of hypoxia?inducible factor?1alpha (HIF?1alpha) and its regulatory enzyme HIF poly l hydroxylase 2 in neonatal rat brain[J].Neurosci Lett, 2006, 404(1?2): 72?77.

百度搜索“77cn”或“免费范文网”即可找到本站免费阅读全部范文。收藏本站方便下次阅读，免费范文网，提供经典小说医药类HIF1α在脑损伤中的作用及其机制的研究进展(3)在线全文阅读。