Biliverdin administration regulates the microRNA-mRNA expressional network associated with neuroprotection in cerebral ischemia reperfusion injury in rats
Biliverdin administration regulates the microRNA-mRNA expressional network associated with neuroprotection in cerebral ischemia reperfusion injury in rats
复制标题
胆绿素调节与大鼠脑缺血再灌注损伤神经保护相关的 microRNA-mRNA 表达网络
DOI：
10.3892/ijmm.2019.4064
复制
发表时间：
2019-03-01
影响因子：
5.4
通讯作者：
Shao, Jian-Lin
中科院分区：
文献类型：
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作者：
Zou, Zhi-Yao;Liu, Jia;Shao, Jian-Lin
炎症反应对脑缺血再灌注损伤（CIR）的预后有重要影响。胆绿素（BV）可减轻大鼠的CIR，但机制尚不清楚。本研究旨在探讨BV给药后cirr大鼠microRNA -mRNA的表达网络。建立BV治疗大鼠大脑中动脉闭塞模型。采用神经系统严重程度评分（NSS）评估大鼠神经行为后，采用微阵列技术分析脑缺血和BV处理后大脑皮层miRNA和mRNA的表达谱。然后利用生物信息学预测筛选miRNA与mRNA的相关性，通过逆转录-定量聚合酶链反应对20个候选miRNA和33个候选mRNA进行验证。通过荧光素酶法检测ETS原癌基因1 （Ets1）与miRNA204-5p的调控关系。与其他组相比，BV组共有86个mirna差异表达。共鉴定出10个mirna和26个候选基因为核心的“microRNA-mRNA”调控网络，该网络与BV给药后CIR大鼠功能改善有关。最后，荧光素酶检测结果证实miRNA204-5p直接靶向Ets1。目前的研究结果表明，BV可能通过影响细胞增殖、凋亡、维持ATP稳态和血管生成来调节多种mirna和mrna，从而改善cirr大鼠的神经行为。
Inflammatory response has an important role in the outcome of cerebral ischemia reperfusion injury (CIR). Biliverdin (BV) administration can relieve CIR in rats, but the mechanism remains unknown. The aim of the present study was to explore the expressional network of microRNA (miRNA)-mRNA in CIR rats following BV administration. A rat middle cerebral artery occlusion model with BV treatment was established. After neurobehavior was evaluated by neurological severity scores (NSS), miRNA and mRNA expressional profiles were analyzed by microarray technology from the cerebral cortex subjected to ischemia and BV administration. Then, bioinformatics prediction was used to screen the correlation between miRNA and mRNA, and 20 candidate miRNAs and 33 candidate mRNAs were verified by reverse transcription-quantitative polymerase chain reaction. Furthermore, the regulation relationship between ETS proto-oncogene 1 (Ets1) and miRNA204-5p was examined by luciferase assay. A total of 86 miRNAs were differentially expressed in the BV group compared with the other groups. A total of 10 miRNAs and 26 candidate genes were identified as a core 'microRNA-mRNA' regulatory network that was linked with the functional improvement of BV administration in CIR rats. Lastly, the luciferase assay results confirmed that miRNA204-5p directly targeted Ets1. The present findings suggest that BV administration may regulate multiple miRNAs and mRNAs to improve neurobehavior in CIR rats, by influencing cell proliferation, apoptosis, maintaining ATP homeostasis, and angiogenesis.