Cao Cao, Deng Fumou, Hu Yanhui
Department of Anesthesiology, Donghu District, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006 Jiangxi China.
3 Biotech. 2020 Apr;10(4):176. doi: 10.1007/s13205-020-2163-0. Epub 2020 Mar 24.
Circular RNA (circRNA) has been well studied in many diseases, whereas their role in patients with postoperative cognitive dysfunction (POCD) remains largely unclear. Here, we investigated the therapeutic effects of dexmedetomidine (Dex) on POCD and analyzed the role of circRNA as well as the pathways that may be involved. The Morris water maze test demonstrated that POCD rats have a longer incubation period than the normal group, but the latency of POCD rats was significantly lower after Dex treatment. Moreover, HE staining showed that Dex improved hippocampal pathological changes. RNA sequencing showed 164 differentially expressed circRNAs between POCD and Dex groups; 74 were upregulated and 90 were downregulated in the Dex group. A total of 20,790 target genes for differentially expressed circRNAs were observed in RNAhybrid and Miranda databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the target genes of differentially expressed circRNAs are mainly focused on positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage, negative regulation of cell adhesion mediated by integrin, and response to cytokines and other function of life activities and involved in the P53 signaling pathway and nuclear factor kappa B (NF-κB) signaling pathway. Furthermore, the expression of five candidate circRNAs (circ-Shank3, circ-Cdc42bpa, circ-chrx-24658, cir-chr17-3642 and circ-Sgsm1) and target genes were consistent with the RNA sequencing results, which was verified by quantitative real-time polymerase chain reaction (qRT-PCR). These results indicate that circ-Shank3 participate in the process of Dex improved POCD through regulating the P53 and NF-κB signaling pathways and may potentially facilitate POCD treatment through the development of clinical drugs.
环状RNA（circRNA）在许多疾病中已得到充分研究，但其在术后认知功能障碍（POCD）患者中的作用仍不清楚。在此，我们研究了右美托咪定（Dex）对POCD的治疗效果，并分析了circRNA的作用以及可能涉及的途径。莫里斯水迷宫试验表明，POCD大鼠的潜伏期比正常组更长，但Dex治疗后POCD大鼠的潜伏期显著缩短。此外，苏木精-伊红（HE）染色显示Dex改善了海马病理变化。RNA测序显示POCD组和Dex组之间有164种差异表达的circRNA；Dex组中74种上调，90种下调。在RNAhybrid和Miranda数据库中观察到差异表达circRNA共有20790个靶基因。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，差异表达circRNA的靶基因主要集中在对DNA损伤的内源性凋亡信号通路的正调控、整合素介导的细胞黏附的负调控、对细胞因子的反应以及其他生命活动功能，并涉及P53信号通路和核因子κB（NF-κB）信号通路。此外，5种候选circRNA（circ-Shank3、circ-Cdc42bpa、circ-chrx-24658、cir-chr17-3642和circ-Sgsm1）及其靶基因的表达与RNA测序结果一致，这通过定量实时聚合酶链反应（qRT-PCR）得到验证。这些结果表明，circ-Shank3通过调节P53和NF-κB信号通路参与Dex改善POCD的过程，并可能通过临床药物开发潜在地促进POCD的治疗。
