Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Laboratory of Anesthesiology, Southwest Medical University, Luzhou, 646000, China.
Curr Med Sci. 2022 Aug;42(4):871-884. doi: 10.1007/s11596-022-2572-x. Epub 2022 Apr 22.
This study aimed to identify microRNAs (miRNAs) involved in the development of perioperative neurocognitive disorders (PND).
Plasma exosomal miRNA expression was examined in patients before and after cardiopulmonary bypass (CPB) using microarray and qRT-PCR and these patients were diagnosed as PND later. Elderly rats were subjected to CPB, and the cognitive functions were examined. Bioinformatics analysis was conducted to predict the targets of miR-214-3p. Rats were administered rno-miR-214-3p agomir before or after CPB to investigate the role of miR-214-3p in PND development.
We identified 76 differentially expressed plasma exosomal miRNAs in PND patients after surgery (P<0.05, ∣log2FC∣>0.58), including the upregulated hsa-miR-214-3p (P=0.002399392). Prostaglandin-endoperoxide synthase 2 (PTGS2) was predicted as a miR-214-3p target. In rats, CPB reduced the platform crossing numbers and target quadrant stay time, accompanied with hippocampal neuronal necrosis. The rno-miR-214-3p level was significantly increased in plasma exosomes but decreased in rat hippocampus after surgery, exhibiting a negative correlation (P<0.001, r=-0.762). A negative correlation between miR-214-3p and PTGS2 protein expression was also observed in the hippocampus after surgery. Importantly, rno-miR-214-3p agomir treatment, before or after surgery, significantly increased the platform crossing numbers (P=0.035) and target quadrant stay time (P=0.029) compared with negative control. Hippocampal PTGS2 protein level was increased in the untreated surgery group and decreased in response to rno-miR-214-3p agomir treatment before or after surgery (both P<0.05 vs. negative control).
These data suggest that miR-214-3p/PTGS2 signaling contributes to the development of PND, serving as a potential therapeutic target for PND.
本研究旨在鉴定围手术期神经认知障碍（PND）发生过程中涉及的 microRNAs（miRNAs）。
使用微阵列和 qRT-PCR 检测心肺旁路（CPB）前后患者血浆外泌体 miRNA 的表达，随后这些患者被诊断为 PND。老年大鼠接受 CPB，检测认知功能。进行生物信息学分析以预测 miR-214-3p 的靶标。CPB 前后给予大鼠 rno-miR-214-3p agomir，以研究 miR-214-3p 在 PND 发展中的作用。
我们鉴定了手术后 PND 患者中 76 种差异表达的血浆外泌体 miRNA（P<0.05，∣log2FC∣>0.58），包括上调的 hsa-miR-214-3p（P=0.002399392）。前列腺素内过氧化物合酶 2（PTGS2）被预测为 miR-214-3p 的靶标。在大鼠中，CPB 降低了平台穿越次数和目标象限停留时间，同时伴有海马神经元坏死。手术后，血浆外泌体中 rno-miR-214-3p 水平显著升高，而大鼠海马中 rno-miR-214-3p 水平降低，呈负相关（P<0.001，r=-0.762）。手术后，海马中 miR-214-3p 与 PTGS2 蛋白表达之间也存在负相关。重要的是，与阴性对照相比，CPB 前后给予 rno-miR-214-3p agomir 治疗显著增加了平台穿越次数（P=0.035）和目标象限停留时间（P=0.029）。未治疗手术组海马 PTGS2 蛋白水平升高，而 rno-miR-214-3p agomir 治疗后降低（均与阴性对照相比，P<0.05）。
这些数据表明，miR-214-3p/PTGS2 信号通路参与了 PND 的发生发展，可能成为 PND 的潜在治疗靶点。
