反复麻醉暴露对幼鼠线粒体功能及认知发育的影响

Impact of repeated anesthesia exposure on mitochondrial function and cognitive development in infant mice

目的观察反复麻醉暴露对幼鼠线粒体功能及认知发育的影响。方法将7日龄幼鼠采用随机数字表法分为4组:对照组、麻醉组、ZLN005组以及ZLN005+麻醉组。建立小鼠的反复麻醉暴露模型,并使用过氧化物酶体增殖物激活受体γ共激活因子-1α(peroxisome proliferator activated receptorγcoactivator-1α,PGC-1α)激动剂ZLN005干预,取幼鼠海马组织检测海马区域总ATP表达水平、线粒体呼吸链复合物主要成分表达水平以及线粒体转录因子A(mitochondrial transcription factor A,mtTFA)表达水平。其余幼鼠于30日龄时检测PSD95表达水平,30-36日龄时进行Morris水迷宫实验,记录逃避潜伏期和穿梭平台次数。对上述指标进行统计学分析。结果与对照组相比,麻醉组在Morris水迷宫定位航行实验的第5、7天逃避潜伏期显著延长(P<0.05;P<0.05),第7天在空间探索实验中穿梭平台次数显著减少(P<0.01),ZLN005组以及ZLN005+麻醉组差异无统计学意义(P>0.05)。与对照组相比,麻醉组海马区域PSD95表达水平、总ATP含量、线粒体基因编码的呼吸链复合物主要成分ND1、COXⅡ、mtTFA的表达均下降,其余两组差异无统计学意义。结论反复麻醉暴露对幼鼠的线粒体功能及认知发育产生不利影响,这种影响主要作用于呼吸链复合物中线粒体基因编码而不是核基因编码的主要成分。

Objective To investigate the effects of repeated anesthesia exposure on mitochondrial function and cognitive development in infant mice.Methods A total of 1047 d-old mice were randomly assigned to 4 groups:control group,anesthesia group,ZLN005 group,and ZLN005+anesthesia group with 26 animals in each group.A repeated anesthesia exposure model was established,and the PGC-1αagonist ZLN005 was used for intervention.At age of 11 d,4 mice were sacrificed in each group and the levels of total ATP,main components of mitochondrial respiratory chain complex,and mitochondrial transcription factor A(mtTFA)expression in the hippocampus of mice were measured.At age of 30 d 4 mice were sacrificed and the expression level of PSD95 were detected.Morris water maze test was performed at 30 to 36 d of age,and the escape latency and the number of shuttle platforms were recorded.Results Compared to the control group,the anesthesia group exhibited significantly prolonged escape latency in Morris water maze navigation test on d5 and d7(P<0.05;P<0.05);and a significant reduction in the number of shuttle platforms of the space exploration test on d7(P<0.01).There was no significant difference between the control group and ZLN005 group,ZLN005+anesthesia group(P>0.05).Compared with the control group,the anesthesia group had a decreased PSD95 expression,total ATP content in the hippocampal region,and the expression of ND1,COXII,and mtTFA,while there was no significant difference between control group and the other two groups.Conclusion Repeated exposure to anesthesia has a negative impact on mitochondrial function and cognitive impairment in infant mice,which primarily affects the major components of the respiratory chain complex encoded by mitochondrial genes rather than nuclear genes.