| 王 月,段博阳,余 莉,吴 德,唐久来.脂多糖对孤独症大鼠行为学发育的影响及病理机制[J].中国康复医学杂志,2022,(9):1158~1164 |
| 脂多糖对孤独症大鼠行为学发育的影响及病理机制 点此下载全文 |
| 王 月 段博阳 余 莉 吴 德 唐久来 |
| 安徽医科大学第一附属医院儿科，安徽省合肥市，230022 |
| 基金项目：国家自然科学基金资助项目（81472167） |
| DOI：10.3969/j.issn.1001-1242.2022.09.002 |
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| 摘要： |
| 摘要
目的：探讨发育早期感染对孤独症症状的影响，建立丙戊酸钠SD大鼠孤独症样模型，分析发育早期脂多糖暴露对其孤独症样行为的影响及病理机制。
方法：随机选取9只SD孕鼠中的6只于孕12.5天给予丙戊酸钠600mg/kg腹腔注射建立孤独症模型，另外3只孕鼠作为对照组，给予生理盐水腹腔注射。模型组孕鼠产仔后，第20天随机挑选一半仔鼠作为丙戊酸钠加脂多糖组，给予脂多糖2mg/kg腹腔注射，另一半生理盐水腹腔注射作为丙戊酸钠组， 注射生理盐水的孕鼠的子代为对照组。采用随机数字法在3组中随机选取仔鼠各8只，在生后43天进行旷场实验、埋珠实验、Y型迷宫实验和三箱社交实验。生后50天3组仔鼠额叶脑组织进行HE染色和透射电镜病理检测，海马组织进行HE染色。
结果：旷场实验、埋珠实验、Y型迷宫实验、三箱实验结果显示，丙戊酸钠组较对照组的活动总距离长、跨格子数多、埋珠个数多、关闭臂进入次数少、关闭臂探索路程少、关闭臂探索时间少、社交性和社交偏好性降低（P<0.05）；丙戊酸钠加脂多糖组较丙戊酸钠组的活动总距离长、跨格子数多、埋珠个数多、关闭臂进入次数少、关闭臂探索路程少、社交性和社交偏好性降低（P<0.05）。HE和电镜结果显示，丙戊酸钠加脂多糖组细胞核膜破裂，较丙戊酸钠组细胞结构损伤更为严重。
结论：发育早期脂多糖注射会使孤独症大鼠模型孤独症样行为加重，提示感染可能是导致孤独症谱系障碍儿童症状恶化的原因之一，值得临床关注。 |
| 关键词：孤独症谱系障碍 脂多糖类 丙戊酸钠 动物行为学 |
| Effects of lipopolysaccharide on behavioral development and pathological mechanism of autism rats Download Fulltext |
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| The First Affiliated Hospital of Anhui Medical University， Hefei， Anhui， 230022 |
| Fund Project: |
| Abstract: |
| Abstract
Objective：To investigate the influence of infection in early development on autism behavior by establishing the model of sodium valproate SD rats and intraperitoneal injection with lipopolysaccharide（LPS）.
Method：12.5 days after conception, six of 9 SD rats were randomly selected to receive 600mg/kg sodium valproate intraperitoneal injection in order to establish autism model， and the other three pregnant rats were given normal saline intraperitoneal injection as the control group. On the 20th day after birth， 3 of the young rats in the model group were randomly selected to receive 2mg/kg lipopolysaccharide intraperitoneal injection as sodium valproate plus lipopolysaccharide group， and the other 3 were intraderitoneal injection of normal saline as sodium valproate group， and the offspring of control group were injected with normal saline. Eight young mice were randomly selected from each of the three groups by random number method. 43 days after birth， open field test， marble burying test， Y-maze test and three-box social test were conducted. 50days after birth， HE staining and transmission electron microscopy were performed on the frontal brain tissues of the three groups， hippocampal tissue was stained with HE.
Result：Compared with the control group， the results of the open field test， marble burying test， Y-maze test and three-box social test showed that the total activity distance of sodium valproate group was longer. The number of cross cells was more， the number of buried beads was more， the number of closed arm entry was less， the closed arm exploration distance was less， the closed arm exploration time was less， and the sociability and social preference were lower in the sodium valproate group （P<0.05）. Compared with the sodium valproate group， the total distance of activity was longer， the number of cross cells was more， the number of buried beads was more， the number of closed arm entry was less， the length of closed arm exploration was less， and the sociability and social preference were lower in the sodium valproate plus lipopolysaccharide group （P<0.05）. The results of HE and electron microscopy showed that the nuclear membrane rupture in the group of sodium valproate plus lipopolysaccharide is more serious than in the sodium valproate group.
Conclusion：Injection of lipopolysaccharide at early stage of development can aggravate the autistic behavior in rats with autism， suggesting that infection may be one of the reasons for the deterioration of symptoms in children with ASD， which deserves clinical attention. |
| Keywords:autism spectrum disorder lipopolysaccharides sodium valproate ethology |
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