Wang Xinlei, Ding Guoyou, Lai Wei, Liu Shiwen, Shuai Jun
Department of Anesthesia, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Department of Anesthesia, Chinese People's Liberation Army No. 94 Hospital, Nanchang, Jiangxi 330002, P.R. China.
Exp Ther Med. 2018 Apr;15(4):3181-3188. doi: 10.3892/etm.2018.5838. Epub 2018 Feb 5.
Anesthesia-induced cognitive impairment is a recognized clinical phenomenon. The present study aimed to investigate the effect of microRNA-383 (miR-383) expression on propofol-induced learning and memory impairment. In total, 48 male Sprague-Dawley rats (weight, 250±10 g) were randomly divided into four groups (n=12 each): Control group, and three groups of rats that were anesthetized with propofol for 6 h and untreated (propofol model group), treated with a constructed lentivirus vector expressing miR-383 mimics (mimic + propofol group), or treated with miR-383 scramble (scramble + propofol group). The learning memory ability, hippocampal neuron apoptosis and expression of apoptosis-associated factors were detected using reverse transcription-quantitiative polymerase chain reaction and western blot analysis. Propofol treatment significantly reduced the relative mRNA and protein expression of miR-383, induced neuron apoptosis, upregulated the Bax/Bcl-2 ratio, downregulated the relative mRNA and protein expression levels of postsynaptic density protein 95 and cAMP-response element binding protein, and inactivated the phosphoinositide 3-kinase/protein kinase B signaling pathway. By contrast, miR-383 mimics significantly altered the propofol-induced dysregulation of the aforementioned factors. In conclusion, miR-383 mimic was able to repair propofol-induced cognitive impairment via protecting against hippocampal neuron apoptosis and dysregulation of related factors. The present study suggested that miR-383 may be used as a potential therapeutic target for the clinical treatment of cognitive impairment induced by propofol anesthesia.
麻醉诱导的认知功能障碍是一种公认的临床现象。本研究旨在探讨微小RNA-383（miR-383）表达对丙泊酚诱导的学习和记忆障碍的影响。总共48只雄性Sprague-Dawley大鼠（体重，250±10 g）被随机分为四组（每组n = 12）：对照组，以及三组用丙泊酚麻醉6小时且未治疗的大鼠（丙泊酚模型组）、用构建的表达miR-383模拟物的慢病毒载体治疗的大鼠（模拟物+丙泊酚组）或用miR-383乱序序列治疗的大鼠（乱序序列+丙泊酚组）。使用逆转录-定量聚合酶链反应和蛋白质免疫印迹分析检测学习记忆能力、海马神经元凋亡及凋亡相关因子的表达。丙泊酚处理显著降低了miR-383的相对mRNA和蛋白表达，诱导神经元凋亡，上调Bax/Bcl-2比值，下调突触后致密蛋白95和环磷酸腺苷反应元件结合蛋白的相对mRNA和蛋白表达水平，并使磷脂酰肌醇3-激酶/蛋白激酶B信号通路失活。相比之下，miR-383模拟物显著改变了丙泊酚诱导的上述因子的失调。总之，miR-383模拟物能够通过防止海马神经元凋亡和相关因子失调来修复丙泊酚诱导的认知障碍。本研究表明，miR-383可能作为丙泊酚麻醉诱导的认知障碍临床治疗的潜在治疗靶点。
