实验动物科学 ›› 2021, Vol. 38 ›› Issue (3): 47-.

• 研究报告 • 上一篇    下一篇

不同干预方式对 ASD 大鼠认知能力的影响及机制探讨

  

  1. ( 1. 广西幼儿师范高等专科学校,南宁 530000) ( 2. 海南科技职业大学,海口 570000)

  • 出版日期:2021-08-06 发布日期:2021-08-23

Effects of Different Interventions on Cognitive Ability in ASD Rats and Possible Mechanisms 

  1. ( 1. Guangxi College for Preschool Education, Nanning 530000, China)
    ( 2
    . Hainan Vocational University of Science and Technology, Haikou 570000, China)

  • Online:2021-08-06 Published:2021-08-23

摘要:

摘要:目的 观察有氧运动丰富环境及二者结合对孤独症谱系障碍( ASD) 大鼠认知功能和海马组织中 ASD 易感基因 NRXN1、NL3 Shank3 表达的影响,探讨其纠正自闭症异常行为的效果及其可能机制方法 采用向 Wistar孕鼠腹腔注射丙戊酸钠建立 ASD 大鼠模型,选取 40 只成功建模的子代大鼠随机分为有氧运动组丰富环境组有氧+环境组以及 ASD 模型组,每组 10 ;在常规饲养的母鼠所产子代中随机挑选 10 只作为空白对照组有氧运动组大鼠接受持续 8 、6 / 每次在同一时间段持续 90 min 的游泳运动干预;丰富环境组大鼠饲养于内有各种玩具可供大鼠嬉戏玩耍的丰富环境饲养笼;运动+环境组接受运动干预,同时在丰富环境中饲养;ASD 模型组和空白对照组不予干预干预后,采用旷场实验和 Morris 水迷宫实验观察其行为学表现与改变;采用 Western blot 检测大鼠海马组织中 NRXN1、NL3 Shank3 蛋白表达情况;采用 RT-PCR 检测大鼠海马组织中 NRXN1、NL3 Shank3mRNA 表达水平结果 与空白组比较,ASD 模型组有氧运动组丰富环境组及有氧 +环境组的穿格次数少( P<0. 05) 、逃避潜伏期长( P<0. 05) 、原平台象限活动时间缩短( P<0. 05) ,NL3、NRXN1 Shank3 蛋白的 mRNA 表达均明显降低( P<0. 05) ;ASD 模型组比较,有氧运动组丰富环境组及有氧+环境组的穿格次数明显增加( P<0. 05) 、逃避潜伏期明显缩短( P<0. 05) 、原平台象限活动时间延长( P<0. 05) ,大鼠海马组织中 NL3、NRXN1、Shank3蛋白的 mRNA 表达均明显升高( P<0. 05,有氧+环境组 P< 0. 01) ;有氧运动组丰富环境组及有氧+环境组相互比较,其穿格次数逃避潜伏期原平台象限活动时间与 NL3、NRXN1 Shank3 蛋白的 mRNA 表达均无显著性差异( P>0. 05) 。 结论 有氧运动丰富环境及二者结合均可提高丙戊酸钠诱导的 ASD 模型大鼠的认知能力,一定程度纠正其异常行为,有氧运动结合丰富环境的干预效果优于单纯的有氧运动单纯的有氧运动优于单纯的丰富环境其作用机制可能与 NRXN-NLGN-SHANK 通路有关

Abstract:

Abstract: Objective Observe the effects of aerobic exercise, enriched environment and their combination on cognitive function and expression of NRXN1, NL3 and Shank3 in hippocampus of rats with ASD, to explore the effect and possible mechanism of it on correcting autistic abnormal behavior. Method ASD RAT models were established by intraperitoneal injection of VPA into pregnant Wistar rats. Forty offspring rats were randomly divided into aerobic exercise group, enriched environment group, exercise + environment group and ASD model group with 10 rats in each group. A total of 10 rats were randomly selected as the control group. The Rats in the aerobic exercise group received swimming exercise intervention lasting 8 weeks, 6 times per week, each time in the same time period, lasting 90 minutes, and the rats in the enriched environment group were kept in an enriched environment cage with various toys for playing. The exercise + environment group received exercise intervention and was raised in enriched environment, while the ASD model group and the control group did not. The behavioral changes were observed by open field test and Morris water maze test, and the expressions of NRXN1, NL3 and Shank3 protein were detected by western blot the mRNA expression levels of NRXN1, NL3 and Shank3 in rat hippocampus were detected by RT-PCR. Result Compared with the control group, ASD model group, aerobic exercise group, enriched environment group and aerobic + enriched environment group had fewer perforation times ( P<0. 05) , longer escape latency ( P<0. 05) , shorter activity time of the original platform quadrant ( P<0. 05) , lower mRNA expression of NRXN1 and Shank3 ( P < 0. 05) . Compared with the ASD model group, the crossing
times of aerobic exercise group, enriched environment group and exercise + environment environment group were significantly increased ( all P<0. 05) , the escape latency was significantly shortened ( P<0. 05) , the activity time of the original plateau quadrant was increased ( P<0. 05) , and the mRNA expression of NR3, NRXN1 and Shank3 were significantly increased ( P < 0. 05, P < 0. 01) . There was no significant difference between aerobic exercise group, enriched environment group and exercise+environment environment group in crossing times, escape latency and activity time of plateau quadrant and NL3, NRXN1 and Shank3 mRNA expression ( P>0. 05) . Conclusion Aerobic exercise, enriched environment and the combination of both can improve the cognitive ability and correct abnormal behavior of ASD rats induced by VPA, the intervention effect of aerobic exercise combined with rich environment is better than pure aerobic exercise and pure aerobic exercise than pure rich environment. Its mechanism of action may be related to the NRXN-NLGN-SHANK pathway.