摘要目的:评价脓毒症小鼠远期认知功能障碍与海马CA1区锥体神经元电活动的关系。方法:选择无特定病原体级雄性C57BL/6J小鼠36只，体重20~25 g，8~10周龄，于海马CA1区植入16通道微电极阵列(MEA)，采用随机数字表法分为2组：假手术组(Sham组， n＝12)和盲肠结扎穿孔组(CLP组， n＝24)。于造模后28~30 d分别采用旷场实验、新物体识别实验和Y迷宫实验评估小鼠认知功能。分别于造模前1 d和旷场实验、新物体识别实验和Y迷宫实验期间，记录海马CA1区锥体神经元尖峰放电频率。采用Pearson相关分析评价海马CA1区锥体神经元尖峰放电频率与认知功能各指标的相关性。 结果:与Sham组比较，CLP组旷场中央区停留时间百分比降低，新物体探索次数和识别指数均降低，进入新臂次数和新臂偏好指数均降低( P<0.05)。与造模前1 d比较，CLP组旷场实验期间海马CA1区锥体神经元尖峰放电频率增加( P<0.05)。新物体识别实验和Y迷宫实验期间，与训练期比较，CLP组测试期海马CA1区锥体神经元尖峰放电频率差异均无统计学意义( P>0.05)。与Sham组比较，CLP组训练期海马CA1区锥体神经元尖峰放电频率增加( P<0.05)，测试期差异无统计学意义( P>0.05)。2组海马CA1区锥体神经元尖峰放电频率与旷场中央区停留时间百分比、新物体识别指数和新臂偏好指数均呈负相关( P<0.05)。 结论:脓毒症小鼠远期认知功能障碍发生机制可能与海马CA1区锥体神经元尖峰放电频率增加有关。

abstractsObjective:To evaluate the relationship between long-term cognitive dysfunction and the electrical activity of pyramidal neurons in the hippocampal CA1 region of septic mice.Methods:Specific pathogen-free male C57BL/6J mice, weighing 20-25 g, aged 8-10 weeks, in which a 16-channel microelectrode array was implanted into the hippocampal CA1 region, were divided into 2 groups using a table of random numbers: sham operation group (Sham group, n=12) and cecal ligation and puncture group (CLP group, n=24). The cognitive function was evaluated using the open field test, novel object recognition test, and Y-maze test at 28-30 days after establishing the model. The spike discharge frequency of pyramidal neurons in the hippocampal CA1 region was recorded on 1 day before establishing the model and during the open field test, novel object recognition test and Y-maze test. Pearson correlation analysis was used to evaluate the correlation between the spike discharge frequency of pyramidal neurons in the hippocampal CA1 region and each cognitive function index. Results:Compared with Sham group, the percentage of time spent in the central area of the open field was significantly decreased, the number of exploring a novel object and novel object recognition index were decreased, the number of entries into novel arm and the preference index for novel arms were decreased in CLP group ( P<0.05). Compared with that at 1 day before establishing the model, the spike discharge frequency of pyramidal neurons in the hippocampal CA1 region during the open field test was significantly increased in CLP group ( P<0.05). During the novel object recognition test and Y-maze test, there was no significant difference in the spike discharge frequency of pyramidal neurons in the hippocampal CA1 region between the test phase and the training phase in CLP group ( P>0.05). Compared with Sham group, the spike discharge frequency of pyramidal neurons in the hippocampal CA1 region was significantly increased during the training phase ( P<0.05), and no significant change was found during the test phase in CLP group ( P>0.05). The spike discharge frequencies of pyramidal neurons in the hippocampal CA1 region were negatively correlated with the percentage of time spent in the central area of the open field, the novel object recognition index, and the preference index for novel arms in both groups ( P<0.05). Conclusions:The mechanism underlying the long-term cognitive dysfunction may be related to the increased frequency of spike discharges in pyramidal neurons in the hippocampal CA1 region of septic mice.