长链非编码RNA在新生大鼠缺氧缺血脑组织中的表达  

Long non - coding RNA expression in neonatal rat brain tissue after hypoxic - ischemic injury

作　　者：赵凤艳[1] 屈艺[1] 李世平[1] 刘海婷[1] 张莉[1] 母得志[1] 

机构地区：[1]四川大学华西第二医院儿科,出生缺陷与相关妇儿疾病教育部重点实验室,发育与妇儿疾病四川省重点实验室,成都610041

出　　处：《中华实用儿科临床杂志》2016年第5期376-379,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金（81330016,81300526,81200462,81270724）;国家重点基础发展计划（973计划）（2013CB967404）

摘　　要：目的探讨长链非编码RNA（1ncRNA）在新生大鼠缺氧缺血性脑损伤中的表达情况。方法10日龄sD大鼠分为假手术组和缺氧缺血组，于缺氧缺血24h处死取脑。采用HE染色观察脑组织病理改变，采用芯片技术检测缺氧缺血组和假手术组lncRNA和mRNA的表达，采用实时定量PCR验证芯片数据。对差异表达mRNA进行基因本体论（GO）分析、通路分析和编码-非编码基因共表达网络等生物信息学分析。结果HE染色显示缺氧缺血组脑组织细胞肿胀、结构不清，排列紊乱。芯片数据表明，与假手术组相比，缺氧缺血组脑组织中322个lncRNA和375个mRNA呈差异表达（P〈0．05），实时定量PCR结果与芯片结果一致。GO分析结果表明，上调表达的mRNA主要富集于损伤反应过程，而下调表达的mRNA则主要富集于成体干细胞分裂过程。通路分析结果表明，上调表达的mRNA主要与细胞因子及其受体相互作用通路相关，而下调表达mRNA则主要与轴突导向通路相关。编码-非编码基因共表达网络分析发现，177个lncRNA与炎症、细胞死亡方面的mRNA表达相关（P〈0．05）。结论缺氧缺血导致新生鼠脑组织中lncRNA和mRNA显著改变，lncRNA可能通过与mRNA相互作用参与发育期脑缺氧缺血损伤的病理过程。Objective To investigate the expression of long non- coding RNA （lncRNA） in neonatal rats with hypoxic - ischemic brain damage （HIBD）. Methods SD rats of 10 postnatal days were divided into the sham - operated control and the hypoxic -ischemic （HI） group. At 24 h after HI, the animals were sacrificed. HE staining was used to assess histopathological damage. Microarray was used to detect the expression of lncRNA and mRNA in hypoxic - ischemic and sham control brain. Real - time PCR was used to verify the microarray result. The differentially expressed mRNA was analyzed by gene ontology （ GO）, pathway and coding - noncoding RNA co - expression （CNC） network analysis. Results HE staining showed that cells in HI brains became swollen and disordered with ambiguous ceil struc- ture. Microarray data demonstrated that 322 lncRNAs and 375 mRNAs were significantly altered in the neonatal brains following hypoxic - ischemic injury compared with sham control （ P 〈 0.05 ）. The real - time PCR results agreed with those of the microarray. GO analysis showed that the most enriched biological process associated with the upregulated mRNA had response to wounding,whereas the biological process mostly enriched among the downregulated mRNA was so- matic stem cell division. Pathway analysis indicated that upregulated mRNA was primarily corresponded with cytokine - cytokine receptor interaction pathway and that downregulated mRNA mainly correlated to axon guidance pathway. CNC network analysis demonstrated that 177 lncRNAs were correlated to the expression of mRNA involved in inflarmnation and cell death （P 〈 0.05）. Conclusions HI injury significantly influences cerebral lncRNA and mRNA expression profiles in the neonatal rat brains. Deregulated lncRNAs might contribute to the pathogenesis of HIBD via interacting with mRNA.

关 键 词：长链非编码RNA 大鼠 新生 缺氧缺血 

分 类 号：R743[医药卫生—神经病学与精神病学]