Changes in expressions of vascular endothelial growth factor and inducible nitric oxide synthase protein in neonatal rats with white matter damage.

Abstract

Abstract: Objective To observe the expressions of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase(iNOS) protein in the brains of premature rats to moderate hypoxia-ischemia (HI),in order to explore possible relationships with white matter damage(WMD). Methods The 3 days old rats were randomly divided into experiment group and sham operation group.The pups were perfused at 12,24,48,72 h and 7 d of recovery from HI.Immunohistochemical technical was applied to investigate the changes of expressions of VEGF and iNOS in periventricular rats white matter tissues. Results In the experiment group,the expression of VEGF in periventricular rats white matter started to increase at 12 h and reached the peak at 24 h.The expression of iNOS was up-regulated at 12 h and peaked at 72 h after HI. Conclusion HI could induce the prominent increase in the expressions of VEGF and iNOS in white matter of the neonatal rats' brain,and may be involved in the pathophysiological process in the WMD.

Key words: white matter damage, hypoxia-ischemia, vascular endothelial growth factor, inducible nitric oxide synthase, neonatal rat

摘要： 目的研究缺氧缺血(HI)对新生大鼠脑白质细胞血管内皮生长因子(VEGF)及诱导型一氧化氮合酶(iNOS)表达的影响,探讨VEGF及iNOS在新生大鼠脑白质损伤(WMD)发病机制中的作用。方法将3日龄大鼠随机分为实验组及假手术组,建立新生大鼠WMD模型,分别予HI后12、24、48、72 h及7 d处死,对其脑组织取材后行HE染色观察其病理改变,并应用免疫组织化学法检测其VEGF及iNOS的表达水平。结果在新生大鼠脑白质中,1)VEGF表达水平予HI后12 h开始明显上升,24 h后达高峰,至7 d恢复正常,与对照组比较,实验组脑室周围白质VEGF的表达在12、24、48、72 h有统计学意义。2)实验组iNOS于HI后12 h表达开始增加,72 h达高峰,7 d仍有表达,与对照组比较,差异有统计学意义。结论 HI可导致新生大鼠脑白质VEGF及iNOS的表达水平显著增高,参与新生大鼠WMD的病理生理过程。

关键词: 脑白质损伤, 缺氧缺血, 血管内皮生长因子, 诱导型一氧化氮合酶, 新生大鼠

CLC Number:

Q426
R722.1

CHANG Xiao,TANG Cheng-he,CAO Yin-li,SHANG Yun,SHI Ji-peng,JIN Jian-yun.. Changes in expressions of vascular endothelial growth factor and inducible nitric oxide synthase protein in neonatal rats with white matter damage.[J]. journal1, 2013, 21(3): 276-279.

常晓,唐成和,曹银利,尚云,石计朋,金建云. 脑白质损伤新生大鼠VEGF及iNOS表达变化研究[J]. 中国儿童保健杂志, 2013, 21(3): 276-279.

References

[1] 刘红梅,李芳军.VEGF与缺血缺氧性脑损伤[J].现代生物医学进展,2009,9(18):3576-3577.
[2] 沈盈,俞惠民.一氧化氮及诱导型一氧化氮合酶与早产儿脑室周围白质软化[J].国际儿科学杂志,2006,33(1):55-57.
[3] Back SA,Riddle A,McClure MM.Maturation-dependent vulnerability of perinatal white matter in premature birth[J].Stroke,2007,38(2):724-730.
[4] Hagberg H,Peebles D,Mallard C.Modles of white matter injury:comparison of infectious,hypoxic-ischemic and excitotoxic insults[J].Ment Retard Dev Disabil Res Rev,2002,8(1):30-38.
[5] Craig A,Luo NL,Beardsley DJ,et al.Quantitative ananysis of perinatal rodent oligodendrocyte lineage progression and its correlation with human[J].Exp Neurol,2003,181(2):231-240.
[6] 朱丽华,蒋犁.缺氧缺血致低龄大鼠脑白质损伤和神经功能障碍的实验研究[J].临床儿科杂志,2007,25(9):784-787.
[7] Ferrara N,Henzel WJ.Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells[J].Biochem Biophys Res Commum,1989,161(2):851-858.
[8] 孙桂莲,杨志亮.新生大鼠缺氧缺血性脑损伤时脑细胞VEGF的表达与凋亡的关系[J].中国医科大学学报,2011,40(6):524-527.
[9] Hai J,Li ST,Lin Q,et al.Vascular endothelia growth factor expression and angiogenesis induced by chronic cerebral hypo perfusion in rat brain[J].Neurosugery,2003,53(4):963-972.
[10] 梁云梅,王华.VEGF-A及VEGF-C mRNA在缺氧缺血性脑损伤新生大鼠脑组织中的表达[J].小儿急救医学,2005,12(2):134-136.
[11] Wang Y,Jin K,Mao XO,et al.VEGF-overexpressing transgenic mice show enhanced post-ischemic neurogenesis and neuromigration[J].J Neurosci Res,2007,85(4):740-747.
[12] Li L,Qu Y,Xiong Y,et al.The involvement of phosphoinositid 3-kinase/Akt pathway in the activation of hypoxia-inducible factor-1alpha in the developing rat brain after hypoxia-ischemia[J].Brain Res,2008,1197(4):152-158. [13] Shen Y,Yu HM.Intrauterine infection induced oligodendrocyte injury and inducible nitric oxide synthase expression in the developing rat brain[J].Journal of Perinatal Medicine,2007,35(3):203-209.
[14] 王慧卿,刘忠强,肖东琼,等.脑白质损伤新生大鼠转录因子-KB和诱导型一氧化氮合酶表达的变化[J].实用儿科临床杂志,2012,27(2):87-90.
[15] 王慧卿,熊英,郭文俊.新生大鼠脑白质损伤时神经胶质细胞凋亡与iNOS 的表达[J].中国当代儿科杂志,2011,13(4):309-312.