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重组人促红细胞生成素对大鼠急性创伤性脑损伤脑组织中基质金属蛋白酶-9及水通道蛋白-4表达的影响

Effects of rhEPO on expression of MMP-9 and AQP-4 in brain tissues of rats with acute traumatic brain injury
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摘要 目的探讨重组人促红细胞生成素(rhEPO)对大鼠急性创伤性脑损伤的神经保护作用及其机制。方法健康雄性SD大鼠55只随机分为假手术组(n=5)、对照组(n=25)和EPO治疗组(n=25);对照组和治疗组采用改进的Feeney等的方法制作脑创伤模型,EPO治疗组在模型建立后立即腹腔注射rhEPO 5000 U/kg,对照组和假手术组在等时间点给予等量生理盐水。根据伤后处死时间点不同每组再分为5个亚组,即6 h、24 h、48 h、3 d、7 d组,每个亚组5只动物。断头、取脑,行HE染色和免疫组织化学方法检测大脑皮层组织中基质金属蛋白酶-9(MMP-9)及水通道蛋白-4(AQP-4)的表达。结果脑创伤大鼠6 h创伤灶脑组织出现MMP-9和AQP-4的表达。与假手术组比较,差异有统计学意义(P<0.05)。EPO治疗组和对照组相比较MMP-9及AQP-4的表达明显降低(P<0.05)。结论rhEPO对大鼠急性创伤性脑损伤有一定的神经保护作用,其机制可能是通过降低MMP-9及AQP-4的表达来实现的。 Objective To explore the neuroprotective mechanisms of recombinant humam erythropoietin (rhEPO) on the rats after acute traumatic brain injury. Methods Fifty-five healthy adult male SD rats were randomly dividied into sham operation group (n = 5), control group (n = 25) and the EPO treatment group (n = 25). The traumatic brain injury of the latter two groups was induced by Feeney's. rhEPO treatment group underwent intraperitoneal injection of 5000 U/kg rhEPO after the injury. The rats in the control group and the EPO treatment group were redivided into 5 subgroups (6 h,24 h ,48 h, 3 d,7 d groups) of 5 rats each respectively according to different time after the injury. The histology was detected by HE staining, the expression of MMP-9 and AQP4 was detected by immunohistochemical. Results The expression of MMP-9 and AQP-4 in the brain tissue of the injury appeared 6 hours alter trauma and was significantly higher in the injury group than that in the sham operation group (P 〈 0.05). The expression was significantly lower in rhEPO treatment group than that in control group (P 〈 0.05). Conclusion ReCombinant human EPO may be neuroprotective against acute traumatic brain injury in rats, probably by inhibiting the activities of MMP-9 and AQP-4.
作者 周鹏 郝解贺
出处 《中国现代医生》 2012年第3期4-6,共3页 China Modern Doctor
关键词 急性创伤性脑损伤 促红细胞生成素 基质金属蛋白酶-9 水通道蛋白-4 Acute traumatic brain injury Erythropoietin Matrix metalloproteinase-9 Aquaporin-4
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参考文献11

  • 1李季林,陈雪林,盛罗平.MMP-9与颅脑损伤的最新研究进展[J].中华全科医学,2011,9(2):271-272. 被引量:10
  • 2Papadopoulos MC,Krishna S,Verkmall AS,et al. Aquaporin water channel sand brain edema[J]. Mt Sinai J Med,2002,69(4):242-248.
  • 3袁雪松,卞晓星.促红细胞生成素对外伤性脑损伤的保护作用[J].国际神经病学神经外科学杂志,2007,34(4):381-384. 被引量:1
  • 4Chen J,Li Y ,Wang L,et al. Therapeutic benefit of intravenousadministration of bone marrow stromal cells after cercbral ischemia in rats[J]. Stroke, 2001.32(4) : 1005-1011.
  • 5Chen G,Shi JX,Hang CH,et al. Inhibitory effect on cerebral inflammatoryagents that accompany traumatic bra in injury in a ratmodel:a potential neuroprotective mechanism of recombinant humanerythropoietin (rhEPO)[J]. Neurosci Lett,2007,425 (3):177-182.
  • 6Keogh CL,Yu SP,Wei L,et al. The effect of recombinant human erythropoictin on neurovasculature repair after focal ischemic stroke in neonatal rats[J]. Pharmacol Exp Thor, 2007,322 ( 2 ) : 521-528.
  • 7Wang X,Jung J,Asahi M,et al. Efects of matrixmet alloproteinase-9 gelle knock tall nn morphological and motor outcomes after traumaticbrain injury[J]. J Neurosci, 2000,20( 18 ) : 7037-7042.
  • 8Wagner S,Nagel S,Kluge B,et al. Topographically graded postis-chemic presence of metallopmteinases is inhibited by hypothermia[J]. Brain Res, 2003,984( 1/2 ): 63-75.
  • 9Rash JE,Yasumura T,Hudson CS,et al. Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocytc plasma membranes in rat brain and spinal cord[J]. Proe Natl Acad Sci USA, 1998,95 (20):11981-11985.
  • 10Sun MC,Honey CR,Berk C,et al. Regulation of aquaporin-4 in a traumatic brain injury model in ralslJ]. J Neyrosurg,2003,98(3):565- 569.

二级参考文献38

  • 1李金星,朱贤立,李玉,王翀,赵甲山,陈登.大鼠弥漫陸脑损伤阻滞ERK通路下调脑组织MMP-9 mRNA的表达[J].中国临床神经外科杂志,2006,11(5):288-291. 被引量:5
  • 2Rosenberg GA. Matrix metalloprnteinases in neuroinilammation [ J ]. Glia,2002,39 ( 3 ) : 279-291.
  • 3Visse R, Nagase H. Matrix metallopmteinases and tissue inhibitors of metal oproteinases: structure, function, and biochemistry [ J ]. Circ Res,2003,92(8) :827-839.
  • 4Higashida T, Kreipke CW, Rafols JA, et al. The role of hy-poxia-induc- ible factor-lalpha, aquaporin-4, and matrix metalloproteinase-9 in blood-brain barrier disruption and brain edema after traumatic brain injury[ J]. J Neurosurg,2010,6(10) :1162-1168.
  • 5Mori T, Wang X, Aoki T, ct al. Downregulation of matrix metalloprotei- nase-9 and attenuation of edema via inhibition of ERK mitogen activa- ted protein kinase in traumatic brain injury[ J]. J Neurotrauma,2002, 19(11) :1411-1419.
  • 6Jia F, Pan YH, Mao Q,et al. Matrix metalloproteinase-9 expression and protein levels after fluid percussion injury in rats : the effect of injury severity and brain temperature [ J ]. J Neurotrauma, 2010,27 ( 6 ) : 1059-1068.
  • 7Davis GE,Senger DR. Endothelial extracellular matrix:biosymhesis, remodeling,and functions during vascular morphogenesis and necves- sel stabilization[ J]. Circ Res ,2005,97 ( 11 ) : 1093-1107.
  • 8Cunningham LA, Wazel M, Rosenberg GA. Muhiple roles for MMPs and TiMPs in cerebral ischemia[ J]. Glia,2005,50(4) :329-339.
  • 9Baker JE.Erythropoietin mimics ischemic preconditioning.Vascul Pharmacol,2005,42(5-6):233-241.
  • 10Eid T,Brines M.Recombinant human erythropoietin forneuro-protection:what is the evidence? Clin Breast Cancer,2002,3(3):109 -115.

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