Xiong Liu-Lin, Xue Lu-Lu, Al-Hawwas Mohammed, Huang Jin, Niu Rui-Ze, Tan Ya-Xin, Xu Yang, Su Ying-Ying, Liu Jia, Wang Ting-Hua
Department of Anesthesiology, National Traditional Chinese Medicine Clinical Research Base and Western Medicine Translational Medicine Research Center, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan Province, China; School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, South Australia, Australia.
Department of Animal Zoology, Kunming Medical University, Kunming, Yunnan Province, China.
Neural Regen Res. 2020 Jan;15(1):86-95. doi: 10.4103/1673-5374.264469.
A single-nucleotide polymorphism (SNP) is an alteration in one nucleotide in a certain position within a genome. SNPs are associated with disease susceptibility. However, the influences of SNPs on the pathogenesis of neonatal hypoxic-ischemic brain damage remain elusive. Seven-day-old rats were used to establish a hypoxic ischemic encephalopathy model. SNPs and expression profiles of mRNAs were analyzed in hypoxic ischemic encephalopathy model rats using RNA sequencing. Genes exhibiting SNPs associated with hypoxic ischemic encephalopathy were identified and studied by gene ontology and pathway analysis to identify their possible involvement in the disease mechanism. We identified 89 up-regulated genes containing SNPs that were mainly located on chromosome 1 and 2. Gene ontology analysis indicated that the up-regulated genes containing SNPs are mainly involved in angiogenesis, wound healing and glutamatergic synapse and biological processing of calcium-activated chloride channels. Signaling pathway analysis indicated that the differentially expressed genes play a role in glutamatergic synapses, long-term depression and oxytocin signaling. Moreover, intersection analysis of high throughput screening following PubMed retrieval and RNA sequencing for SNPs showed that CSRNP1, DUSP5 and LRRC25 were most relevant to hypoxic ischemic encephalopathy. Significant up-regulation of genes was confirmed by quantitative real-time polymerase chain reaction analysis of oxygen-glucose-deprived human fetal cortical neurons. Our results indicate that CSRNP1, DUSP5 and LRRC25, containing SNPs, may be involved in the pathogenesis of hypoxic ischemic encephalopathy. These findings indicate a novel direction for further hypoxic ischemic encephalopathy research. This animal study was approved on February 5, 2017 by the Animal Care and Use Committee of Kunming Medical University, Yunnan Province, China (approval No. kmmu2019038). Cerebral tissue collection from a human fetus was approved on September 30, 2015 by the Ethics Committee of Kunming Medical University, China (approval No. 2015-9).
单核苷酸多态性（SNP）是指基因组中某一特定位置的一个核苷酸发生改变。SNP与疾病易感性相关。然而，SNP对新生儿缺氧缺血性脑损伤发病机制的影响仍不明确。采用7日龄大鼠建立缺氧缺血性脑病模型。利用RNA测序分析缺氧缺血性脑病模型大鼠的SNP和mRNA表达谱。通过基因本体论和通路分析鉴定并研究了与缺氧缺血性脑病相关的具有SNP的基因，以确定它们可能参与的疾病机制。我们鉴定出89个上调基因含有SNP，这些基因主要位于1号和2号染色体上。基因本体论分析表明，含有SNP的上调基因主要参与血管生成、伤口愈合、谷氨酸能突触以及钙激活氯通道的生物学过程。信号通路分析表明，差异表达基因在谷氨酸能突触、长时程抑制和催产素信号传导中发挥作用。此外，通过PubMed检索和RNA测序对SNP进行高通量筛选的交叉分析表明，CSRNP1、DUSP5和LRRC25与缺氧缺血性脑病最为相关。通过对氧糖剥夺的人胎儿皮质神经元进行定量实时聚合酶链反应分析，证实了基因的显著上调。我们的结果表明，含有SNP的CSRNP1、DUSP5和LRRC25可能参与缺氧缺血性脑病的发病机制。这些发现为进一步研究缺氧缺血性脑病指明了新方向。本动物研究于2017年2月5日获得中国云南省昆明医科大学动物伦理委员会批准（批准号：kmmu2019038）。从人胎儿采集脑组织于2015年9月30日获得中国昆明医科大学伦理委员会批准（批准号：2015-9）。
