目的 观察早产儿脑白质损伤大鼠模型海马组织多肽谱差异表达，探索早产儿脑白质损伤机制。方法 将20只新生Sprague-Dawley大鼠随机分为对照组和模型组（n=10）。模型组幼鼠在生后2 d行右侧颈总动脉永久结扎术，术后缺氧2 h；假手术组幼鼠分离右侧颈总动脉，但不行结扎和缺氧。采集两组大鼠脑组织标本并分离海马组织，采用液相色谱串联质谱联合串联质谱标记法检测两组大鼠海马组织多肽谱，将两组中差异表达多肽进行生物信息学分析，推断其在神经系统发育和功能中的作用。结果 共鉴定并量化4 164条多肽，其中262条多肽存在差异表达（倍数变化绝对值≥ 2.5），164条多肽表达上调，98条多肽表达下调。前体蛋白ELN、PCLO、MYO15a、MAP4和MAP1b的差异表达多肽最多，可能在早产儿脑白质损伤的发病机制中具有重要意义。早产儿脑白质损伤模型大鼠的海马区CDK5信号通路被激活。结论 MAP1b等前体蛋白的差异表达多肽可能是早产儿脑白质损伤过程中参与神经系统发育和功能的关键生物活性多肽，CDK5信号通路激活可能与早产儿脑白质损伤有关。
Abstract
Objective To observe differential peptidomics in the hippocampal tissue in a rat model of premature white matter injury, and to investigate the mechanism of premature white matter injury. Methods Twenty neonatal Sprague-Dawley rats were randomly and equally divided into a control group and a model group. Rats in the model group underwent permanent ligation of the right common carotid artery 2 days after birth, followed by 2 hours of hypoxia. For rats in the control group, the right common carotid artery was isolated, but without ligation and hypoxia. Brain tissue samples were collected from the two groups, and hippocampal tissue was isolated. Liquid chromatographytandem mass spectrometry combined with tandem mass spectrometry was used for peptidomic profiling of hippocampal tissue, and the differentially expressed peptides between the two groups were subjected to bioinformatics analysis to assess their possible roles in neural development and function. Results A total of 4164 peptides were identified and quantified, and 262 of them were differentially expressed (absolute fold change ≥ 2.5), including 164 upregulated peptides and 98 downregulated peptides. The numbers of differentially expressed peptides of the precursor proteins ELN, PCLO, MYO15a, MAP4, and MAP1b were the most, and may play significant roles in the pathogenesis of premature white matter injury. CDK5 signaling pathway in the hippocampus was activated in the rat model of premature white matter injury. Conclusions The differentially expressed peptides related to precursor proteins such as MAP1b may be key bioactive peptides involved in neural development and function in premature white matter injury, and activation of the CDK5 signaling pathway may be associated with premature white matter injury.
关键词
早产儿脑白质损伤 /
多肽组学分析 /
液相色谱串联质谱法 /
大鼠
Key words
Premature white matter injury /
Peptidomics analysis /
Liquid chromatography-tandem mass spectrometry /
Rats
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