术后认知功能障碍小鼠miR-146a表达的变化

Changes of miR-146a expression in postoperative cognitive dysfunction mice

目的观察术后认知功能障碍(postoperative cognitive dysfunction,POCD)小鼠术后血清、海马及前额叶皮质中miR-146a表达的变化。方法雄性C57BL/6小鼠50只,12~14周龄,体重25~30g,采用随机数字表法将其分为两组:对照组(C组)和麻醉手术组(AS组),每组25只。AS组在2.1%异氟醚吸入麻醉下行胫骨骨折开放复位内固定术,C组不行麻醉和手术处理。于术前24h及术后6、12、24、48h每组分别取3只小鼠进行摘眼球取血,处死后取海马和前额叶皮质,采用RT-PCR法测小鼠血清、海马和前额叶皮质中miR-146a表达量。于术后第1、3、7天每组各取10只小鼠,进行场景恐惧记忆实验和声音提示恐惧记忆实验,记录僵直时间百分比。结果与C组比较,AS组场景恐惧记忆实验中僵直时间百分比明显降低(P<0.05),声音提示恐惧记忆实验中两组僵直时间百分比差异无统计学意义。在血清中,与C组比较,术后6、12、24、48h AS组miR-146a表达量明显升高(P<0.05);与术后12h比较,术后6、24、48hAS组miR-146a表达量明显降低(P<0.05)。在海马中,与C组比较,术后6、12、24、48h AS组miR-146a表达量明显升高(P<0.05);与术后12h比较,术后6、48h AS组miR-146a表达量明显降低(P<0.05)。在前额叶皮质中,与C组比较,AS组术后24、48h miR-146a表达量明显升高(P<0.05);与术后24h比较,术后48h AS组miR-146a表达量明显升高(P<0.05)。结论 POCD小鼠血清、海马及前额叶皮质中miR-146a表达升高,miR-146a表达量的变化可能与POCD的发病机制相关。

Objective To investigate the changes of miR-146 aexpression in serum,hippocampus and prefrontal cortex in postoperative cognitive dysfunction（POCD）mice.Methods Fifty healthy male C57 BL/6 mice,aged 12-14 weeks,weighing 25-30 g,were randomly divided into two groups（n=25 each）using a random number table：control group（group C）and anesthesia plus surgery group（group AS）.Mice in group AS underwent open tibial fracture of the left hind paw with intramedullary fixation in aseptic conditions under general anesthesia with 2.1% isoflurne.Ten mice in each group received the fear conditioning test（FCT）on the 1,3 and 7 days after anesthesia/surgery.The rest of mice were sacrificed 24 h before（baseline）,and 6,12,24,48 hafter anesthesia/surgery,and then the serum,prefrontal cortex and hippocampus were collected or removed for detection of the expression of miR-146a using quantitative reverse transcription polymerase chain reaction（qRTPCR）.Results Compared with group C,the percentage of freezing time in contextual FCT was significantly decreased（P〈0.05）in group AS,while no significant change in freezing time percentage was found in tone-cued FCT.In serum,compared with group C,miR-146a expression at 6,12,24,48 h after anesthesia/surgery was significantly up-regulated in group AS（P〈0.05）;and in group AS,the expression of miR-146a was significantly decreased 6,24,48 has compared to that at 12 h after anesthesia/surgery（P〈0.05）.In hippocampus,compared with group C,miR-146a expression at 6,12,24,48 h after surgery was significantly up-regulated in group AS（P〈0.05）;and in group AS,the expression of miR-146a at 6,48 h after surgery was significantly decreased as compared to that at 12 hafter anesthesia/surgery（P〈0.05）.In prefrontal cortex,compared with group C,miR-146a expression at 24,48 h after surgery was significantly up-regulated in group AS（P〈0.05）;andin group AS,the expression of miR-146a was significantly increased at 48 h as compared to that at 24 h after anesthesia/surgery（P〈0.05）.Conclusion The expression of miR-146a in serum,hippocampus and prefrontal cortex in POCD mice was up-regulated,and changes of miR-146a expression may be related to the development of POCD.