PDF(Pubmed)
Abstract：
Postoperative cognitive dysfunction (POCD) is a clinical syndrome characterizing by cognitive impairments in the elderly after surgery. There is limited effective treatment available or clear pathological mechanisms known for this syndrome. In this study, a Connectivity Map (CMap) bioinformatics model of POCD was established by using differently expressed landmark genes in the serum samples of POCD and non-POCD patients from the only human transcriptome study. The predictability and reliability of this model were further supported by the positive CMap scores of known POCD inducers and the negative CMap scores of anti-POCD drug candidates. Most retinoic acid receptor (RAR) agonists were negatively associated with POCD in this CMap model, suggesting that RAR might be a novel target for POCD. Most importantly, acitretin, a clinically used RAR agonist, significantly inhibited surgery-induced cognitive impairments and prevented the reduction in RARα and RARα-target genes in the hippocampal regions of aged mice. The study denotes a reliable CMap bioinformatics model of POCD for future use and establishes that RAR is a novel therapeutic target for treating this clinical syndrome.
摘要：
术后认知功能障碍（POCD）是老年人术后认知障碍的临床综合征。对于这种综合征，有效的治疗方法有限或明确的病理机制。在这项研究中,通过使用来自唯一人类转录组研究的POCD和非POCD患者的血清样品中不同表达的标志基因,建立了POCD的连接图(CMap)生物信息学模型。该模型的可预测性和可靠性进一步得到了已知POCD诱导剂的阳性CMap评分和抗POCD药物候选物的阴性CMap评分的支持。在该CMap模型中，大多数视黄酸受体（RAR）激动剂与POCD呈负相关。表明RAR可能是POCD的新靶标。最重要的是,阿维酮,临床上使用的RAR激动剂，显着抑制手术引起的认知障碍，并防止老年小鼠海马区域RARα和RARα靶基因的减少。该研究表明了POCD的可靠CMap生物信息学模型，可供将来使用，并确定RAR是治疗该临床综合征的新治疗靶标。
