全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

Notch信号通路在新生鼠高氧暴露致少突胶质细胞成熟障碍中的作用

, PP. 1766-1770

Keywords: 高氧,DAPT,脑损伤,Notch信号通路,少突胶质细胞成熟

Full-Text   Cite this paper   Add to My Lib

Abstract:

目的探讨Notch信号通路在新生鼠高氧暴露致少突胶质细胞成熟障碍中的作用。方法取C57BL/10J新生3d(P3)小鼠64只,分为空气对照组(C)、空气+DAPT组(C+DAPT)、高氧组(H)、DAPT预处理高氧暴露组(H+DAPT);H组予以高氧暴露48h,H+DAPT组采用Notch信号特异抑制剂DAPT(10mg/kg)腹腔注射1h后高氧暴露48h。生后5d(P5)断头取脑。Real-timePCR检测Notch1、Jagged1、Hes1及Hes5表达变化。生后12d(P12)取脑,HE染色观察脑白质形态学变化;免疫荧光化学染色检测成熟少突胶质细胞表达;Westernblot定量检测MBP蛋白的表达量。结果与C组比较,H组小鼠脑组织明显水肿,Notch1、Jagged1、Hes1及Hes5mRNA的表达均增高(P<0.05);与H组比较,H+DAPT组Notch1、Jagged1mRNA表达明显增强(P<0.05),Hes1及Hes5mRNA表达显著降低(P<0.05);免疫荧光和Westernblot结果均显示H组MBP表达低于C组(P<0.05);而与H组比较,H+DAPT组MBP表达显著增多(P<0.05)。结论Notch信号通路参与了高氧暴露致新生鼠脑白质损伤过程,其机制可能与影响少突胶质细胞的成熟有关。

References

[1]  Gerstner B, Buhrer C, Rheinlander C, et al. Maturation-dependent oligodendrocyte apoptosis caused by hyperoxia[J]. J Neurosci Res, 2006, 84(2):? 306-315. [2]Doyle L W, Roberts G, Anderson P J, et al. Outcomes at age 2 years of infants <28 weeks’ gestational age born in Victoria in 2005[J]. J Pediatr, 2010, 156(1):? 49-53. [3]Ritter J, Schmitz T, Chew L J, et al. Neonatal hyperoxia exposure disrupts axon-oligodendrocyte integrity in the subcortical white matter[J]. J Neurosci, 2013, 33(21):? 8990-9002. [4]Vottier G, Pham H, Pansiot J, et al. Deleterious effect of hyperoxia at birth on white matter damage in the newborn rat[J]. Dev Neurosci, 2011, 33(3/4):? 261-269. [5]Schmitz T, Ritter J, Mueller S, et al. Cellular changes underlying hyperoxia-induced delay of white matter development[J]. J Neurosci, 2011, 31(11):? 4327-4344. [6]Brehmer F, Bendix I, Prager S, et al. Interaction of inflammation and hyperoxia in a rat model of neonatal white matter damage[J]. PLoS One, 2012, 7(11):? e49023. [7]Scheer N, Groth A, Hans S, et al. An instructive function for Notch in promoting gliogenesis in the zebrafish retina [J]. Development, 2001, 128(7):? 1099-1107. [8]Yao L, Kan E M, Kaur C, et al. Notch-1 signaling regulates microglia activation via NF-κB pathway after hypoxic exposure in vivo and in vitro[J]. PLoS One, 2013, 8(11):? e78438. [9]Nasoohi S, Hemmati A A, Moradi F, et al. The γ-secretase blocker DAPT impairs recovery from lipopolysaccharide-induced inflammation in rat brain[J]. Neuroscience, 2012, 210:? 99-109. [10]Park H C, Appel B. Delta-Notch signaling regulates oligodendrocyte specification[J]. Development, 2003, 130(16):? 3747-3755. [11]Castillo A, Sola A, Baquero H, et al. Pulse oxygen saturation levels and arterial oxygen tension values in newborns receiving oxygen therapy in the neonatal intensive care unit:? is 85% to 93% an acceptable range? [J]. Pediatrics, 2008, 121(5):? 882-889. [12]Wang S, Sdrulla A D, diSibio G, et al. Notch receptor activation inhibits oligodendrocyte differentiation[J]. Neuron, 1998, 21(1):? 63-75. [13]王利祥, 华子春. Notch信号通路研究进展[J]. 中国医药生物技术, 2009, 4(3):? 224-226. [14]陈坤, 蒋朴, 徐颖, 等. Toll样受体4在新生小鼠常压高氧脑损伤中的作用[J]. 免疫学杂志, 2012, 28(2):? 98-103. [15]蒋朴, 徐颖, 胡良安, 等. 高浓度氧暴露对N9小胶质细胞功能的影响[J]. 南方医科大学学报, 2012, 32(1):? 71-74. [16]董乐乐, 于泽, 连建强. 髓鞘碱性蛋白临床意义研究进展[J].包头医学院学报, 2012, 28(6):? 139-140.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133