环状RNA在炎症所致早产小鼠脑损伤中的作用及机制初步研究

Role and mechanism of circular RNA in brain injury induced by inflammation in preterm mice: a preliminary study

摘要:

目的 探讨环状RNA（circular RNA，circRNA）及circRNA-微小RNA（microRNA，miRNA）网络调控与炎症诱导早产小鼠脑损伤的关系，为早产儿脑损伤的防治提供依据。方法 以孕鼠腹腔注射脂多糖建立炎症诱导早产小鼠脑损伤模型（炎症早产组，n=3），正常孕鼠剖宫产早产小鼠作为对照（非炎症早产组，n=3）。采用微阵列基因芯片技术筛选早产儿脑损伤相关的circRNA，通过miRNA靶预测软件预测circRNA和miRNA相互作用的结合位点，研究其调控机制。结果 与非炎症早产组比较，炎症早产组显著差异表达的circRNA有365条（差异倍数 > 1.5，P < 0.05），包括差异表达上调206条，差异表达下调159条。对差异表达倍数4倍以上的circRNA行进一步分析，发现这些circRNA可与miRNA结合并调节其活性，从而调控与神经系统相关基因的表达。结论 炎症诱导早产小鼠脑组织circRNA表达谱发生明显变化；circRNA的表达变化可通过调控miRNA的活性在炎症诱导早产小鼠脑损伤及之后的脑发育中发挥作用。

Abstract:

Objective To determine the association of circular RNA (circRNA) and circRNA-microRNA (miRNA) network regulation with brain injury induced by inflammation in preterm mice. Methods Pregnant mice were treated with intraperitoneally injected lipopolysaccharide to establish a preterm mouse model of brain injury induced by inflammation (inflammation preterm group with 3 mice). Preterm mice born to normal pregnant mice by cesarean section were selected as controls (non-inflammation preterm group with 3 mice). The gene microarray technique was used to screen out the circRNAs associated with brain injury in preterm mice. The miRNA target prediction software was used to predict the binding sites between circRNAs and miRNAs and analyze the regulatory mechanism. Results A total of 365 differentially expressed circRNAs were screened out between the inflammation preterm and non-inflammation preterm groups (fold change > 1.5, P < 0.05), among which there were 206 upregulated circRNAs and 159 downregulated circRNAs. Further analysis of the circRNAs with a fold change of > 4 showed that these circRNAs could bind to miRNAs and regulate their activity, thereby regulating the expression of the genes associated with the nervous system. Conclusions Inflammation induces a significant change in the expression profile of circRNAs in the brain tissue of mice, and the change in the expression of circRNAs plays an important role in brain injury induced by inflammation and subsequent brain development in preterm mice.