丰富环境预干预对脓毒性脑病大鼠认知功能的影响

关键词：丰富环境  标准环境  预干预  脓毒性脑病  认知功能障碍

Keywords:environmental enrichment  standard environment  pre-exposure  sepsis-associated encephalopathy  cognitive deficits

摘要：

      摘要 目的：探讨丰富环境（environmental enrichment， EE）预干预对脓毒性脑病（sepsis-associated encephalopathy， SAE）大鼠认知功能的影响，以期为SAE后认知障碍的防治提供新的思路和方法。 方法：选用成年SD大鼠，分为EE预干预+SAE组（EE-SAE组）、标准环境（standard environment， SE）预干预+SAE组（SE-SAE组）、假手术对照组（Sham组），每组各6只大鼠。每组大鼠均接受30天的EE或者SE干预，干预结束后，采用盲肠结扎穿孔法（cecal ligation and perforation， CLP）制作SAE模型。术后分别采用Morris水迷宫（Morris water maze， MWM）、高架十字迷宫（elevated plus-maze test， EPM）、旷场试验（open field test， OFT）、新物体识别试验（novel object recognition test， NORT），以及感觉忽略试验（sensory neglect test， SNT）来评估大鼠的认知功能。 结果：SAE损伤了大鼠的空间学习能力、工作记忆能力、再认记忆能力，以及空间探索能力，同时增加焦虑样行为。而经过EE预干预，SAE所致的上述认知功能障碍能显著减轻：EE-SAE vs.SE-SAE： MWM测试潜伏期（第5天）： P=0.016，平台所在象限时间比例：P=0.0134，穿越平台所在位置次数：P=0.0347；NORT识别指数：P=0.0002；OF跨格次数：P=0.0485，中央格运动时间：P=0.0217，角落格运动时间：P=0.0145。同时，焦虑样行为也显著减少：EE-SAE vs SE-SAE：EPM修饰时间：P=0.0451，进入开臂次数：P=0.0019，进入闭臂次数：P=0.0483，开臂活动时间：P=0.0498。 结论：丰富环境预干预能显著改善SAE大鼠的认知功能，这为预防SAE所致认知功能障碍提供了新的思路。

Abstract:

      Abstract Objective：To investigate the effect of pre-exposure to environmental enrichment （EE） on the cognitive deficits cause by sepsis-associated encephalopathy （SAE）. Method：Sprague Dawley （SD） rats were randomly divided into three groups： pre-exposure to EE + SAE group （EE-SAE group）， pre-exposure to standard environment （SE） + SAE group （SE-SAE group）， sham operation group （Sham group）. The rats in each group received EE or SE housing for 30 days. After housing， SAE model was induced by cecal ligation and perforation （CLP）. And then， the rats were subjected to a behavioral test battery including Morris water maze （MWM）， elevated plus maze （EPM），open field test （OF）， novel object recognition test （NORT） and sensory neglect test （SNT）. The behavioral test battery was used to evaluate the learning and memory capacity. Result：SAE impaired recognition memory， working memory， exploratory activity and increased anxiety-like behavior. These impairments were significantly inhibited in rats receiving pre-exposure to EE （EE-SAE vs SE-SAE：MWM：latency to platform： 5d：P=0.016，time in targeted quadrant（%）：P=0.0134，crossing times：P=0.0347；NORT：discrimination index：P=0.0002；OF：number of line crossings：P=0.0485，time in the center squares：P=0.0217，time in the corner squares：P=0.0145）. In addition， pre-exposure to EE also decreased the SAE-induced anxiety-like behavior （EE-SAE vs SE-SAE：EPM：grooming time：P=0.0451，entries in open arm：P=0.0019，entries in close arm：P=0.0483，open arm time：P=0.0498）. Conclusion：These results support the importance of pre-exposure to EE to prevent cognitive deficits induced by SAE.