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FMRP/mTOR信号级联失调与脑损伤早产儿远期神经发育的关系

2021-03-25李慧玲闵双武司媛王丽阳衣兰云戚家峰

中国医学创新 2021年34期

李慧玲 闵双武  司媛  王丽阳  衣兰云 戚家峰

【摘要】 目的:探究FMRP/mTOR信號级联失调与脑损伤早产儿远期神经发育的关系。方法:选取2019年1月-2021年6月在省妇幼保健院出生的60例缺血缺氧性脑损伤早产儿为脑损伤组,选取同时期在医院生产的无缺血缺氧性脑损伤早产儿60例为对照组。新生儿出生24 h后抽取血液样本用于蛋白印迹分析FMRP/mTOR的表达。通过马伦早期学习量表(MSEL)、皮博迪发育运动量表(PDMS)和Vineland适应性行为量表(VABS)评估新生儿的神经发育。结果:脑损伤组FMRP和磷酸化FMRP蛋白表达均低于对照组,p70S6K和磷酸化p70S6K蛋白表达均高于对照组(P<0.05)。脑损伤组MSEL、PDMS和VABS评分均低于对照组(P<0.05)。结论:FMRP/mTOR通路的失调可能在脑损伤早产儿的发病机制中起作用,会影响幸存者的神经发育功能,因此,FMRP/mTOR信号通路可能是治疗脑损伤早产儿及其神经认知缺陷的一个可能的新分子靶点。

【关键词】 FMRP/mTOR 脑损伤 早产儿 远期神经发育 认知行为功能

Relationship between Long-term Neurodevelopment in Preterm Infants with Brain Injury and FMRP/mTOR Signal Cascade Maladjustment/LI Huiling, MIN Shuangwu, SI Yuan, WANG Liyang, YI Lanyun, QI Jiafeng. //Medical Innovation of China, 2021, 18(34): -130

[Abstract] Objective: To explore the relationship between long-term neurodevelopment of preterm infants with brain injury and FMRP/mTOR signal cascade maladjustment. Method: A total of 60 premature infants with hypoxic-ischemic brain injury born in the Provincial Maternal and Child Health Hospital from January 2019 to June 2021 were selected as the brain injury group, and 60 preterm infants without hypoxic-ischemic brain injury born in the hospital during the same period were selected as the control group. Blood samples were taken at 24 h of birth for Western blot analysis of FMRP/mTOR expression. The neurodevelopment of newborns was evaluated by Marlen scale of early learning (MSEL), Peabody developmental movement scale (PDMS) and Vineland adaptive behavior scale (VABS). Result: The expressions of FMRP and phosphorylated FMRP protein in the brain injury group were lower than those in the control group, and the expressions of p70S6K and phosphorylated p70S6K protein were higher than those in the control group (P<0.05). The scores of MSEL, PDMS and VABS in the brain injury group were lower than those in the control group (P<0.05). Conclusion: The imbalance of FMRP/mTOR pathway may play a role in the pathogenesis of preterm infants with brain injury and affect the neurodevelopmental function of survivors. Therefore, FMRP/mTOR signaling pathway may be a possible new molecular target for the treatment of preterm infants with brain injury and their neurocognitive defects.

[Key words] FMRP/mTOR Brain damage Premature infant Long-term neurodevelopment Cognitive behavioral function

First-author’s address: Harbin Children’s Hospital, Harbin 150010, China

doi:10.3969/j.issn.1674-4985.2021.34.030

近年来,早产儿脑损伤是一个日益受到关注的问题。神经影像学的创新提高了对活婴儿小脑损伤的诊断敏感性[1],这些病变的信号特征表明有明显的出血成分。尽管人们越来越认识到这个问题,但目前关于早产儿脑损伤长期神经发育后果的数据非常有限。迄今为止,结果研究仅限于病例报告或随访时年龄分布广泛的小病例系列,结果通常基于医学图表审查或非正式神经发育评估。早产是导致包括脑瘫在内的长期运动缺陷的一个公认原因[2]。此外,最近关于早产幸存儿长期的研究报告强调了神经发育的问题,包括认知功能障碍、学习和行为障碍[3]。……

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