自发性高血压大鼠延髓microRNA差异表达分析

目的　探讨自发性高血压大鼠延髓microRNA（miRNA）差异表达谱及其靶基因生物信息学分析。 方法　采用自发性高血压大鼠模型（SHR组），同周龄SD大鼠为对照组（Control组）。利用miRNA芯片检测大鼠延髓中miRNAs差异表达谱。 结果　与对照组比较，SHR组尾动脉收缩压显著升高（P＜0.0001）；SHR组延髓组织miRNAs有显著差异表达谱，16个miRNAs表达上调和7个miRNAs表达下调（1.5-fold change cutoff, P<0.05）。qRT-PCR验证结果显示，与对照组比较，SHR组延髓miR-153、miR-193及miR-301a表达显著下降，与芯片结果一致。生物信息学分析显示，差异表达miRNAs可能调控2775个靶基因（target score≥83）。这些靶基因主要富集在12个信号通路，包括磷脂酰肌醇3-激酶（Phosphatidylinositide3-kinase，PI3K）通路等。 结论　自发性高血压大鼠延髓组织中miR-153、miR-193及miR-301a明显下调，且生物信息学分析提示PI3K通路介导神经炎症可能作为高血压中枢相关差异表达miRNAs调控靶基因介导的主要致病通路。

MicroRNA profiling of medulla oblongata in spontaneous hypertensive rats

Objective　To reveal the microRNA (miRNA) profiling of medulla oblongata in spontaneous hypertensive rat (SHR).　Methods　Spontaneous hypertensive rats were taken as the SHR group, and normal blood pressure SD rats were the control group. Microarray analysis was performed to compare the miRNA expression profiles of medulla between the SHR and control group.　Results　Compared with the control group, the systolic pressure of the tail artery of SHR group increased significantly（P<0.0001）. There were significant differential expression profile in the medulla oblongata miRNAs of SHR group, including 16 miRNAs expression up-regulated and 7 miRNAs expression down-regulated (1.5-fold change cutoff, P<0.05). The qRT-PCR data showed that miR-153, miR-193 and miR-301a were significantly down-regulated in medullas of SHRs, which were consistent with the microarray data. From the miRDB online database, we identified 2775 targets for all differentiated miRNAs (target score was set to≥83). The KEGG pathways for these targets were enriched in 12 pathways, including phosphatidylinositide 3-kinase (PI3K) pathway. Conclusion miR-153, miR-193 and miR-301a expression are significantly down-regulated in medulla oblongata of spontaneous hypertensive rats. Bioinformatics analysis suggests that nerve inflammation mediated by PI3K pathway may be the main pathogenic pathway regulated by the differentially expressed miRNAs of hypertension.