丰富环境对缺氧缺血脑损伤幼鼠空间记忆能力及海马区BDNF、自噬相关蛋白LC3表达的影响

Effects of environmental enrichment on the expressions of brain-derived neurotrophic factor and microtu⁃bule-associated protein 1 light chain 3 type in the hippocampus of immature rats with hypoxic-ischemic brain damage

目的:探索丰富环境干预对缺氧缺血脑损伤(HIBD)幼鼠空间记忆能力、海马区脑源性神经营养因子(BDNF)及微管相关蛋白1轻链3(LC3)表达的影响。方法:取7日龄Wistar鼠共32只随机分为假手术组、标准环境组及丰富环境组,采用改良Rice-Vannucci法制备HIBD模型。采用Morris水迷宫定位航行实验测定寻找隐藏平台的逃避潜伏期,采用Western Blot检测海马区BDNF及LC3蛋白的表达。结果:HIBD大鼠寻找平台的逃避潜伏期明显延长,在训练第4、5日丰富环境组逃避潜伏期较标准环境组明显缩短(P<0.01);与标准环境组病灶侧海马相比,丰富环境组病灶侧海马BDNF及LC3-Ⅱ表达显著增高,且LC3-Ⅱ/LC3-Ⅰ比值显著升高(P<0.01)。结论:丰富环境干预可显著改善HIBD幼鼠的空间记忆能力,海马区BDNF表达的上调及自噬信号的激活可能是丰富环境干预有效性的内在机制之一。

Objective:To explore the effects of environmental enrichment intervention on spatial memory ability,the expressions of brain-derived neurotrophic factor(BDNF)and microtubule-associated protein 1 light chain 3 type(LC3)in the hippocampus of immature rats with hypoxic-ischemic brain damage(HIBD).Method:Two kinds of feeding environment were constructed:standard environment and environmental enrichment.Thirty two Wistar rats of seven-day-old were randomized in sham operated group,standard environment group and environmental enrichment group.HIBD models were made by adopting the Rice-Vannucci approach in both standard environment group and environmental enrichment group.The sham operated group and standard environment group were raised in the standard environment all day,while the environmental enrichment group was raised in the environmental enrichment all day.After 14 days of environmental enrichment intervention,the escape latency for searching the hidden platform of immature rats was tested through the orientation navigation experiment of the Morris water maze.The expressions of BDNF and LC3 protein were detected by Western Blot.Result:The escape latency for searching the hidden platform was significantly prolonged in the HIBD rats.On the fourth and fifth days of the Morris water maze test,the escape latency in environmental enrichment group was significantly shorter than that in standard environment group(P<0.01).Compared to the lesion lateral hippocampus in standard environment group,the expressions of BDNF and LC3 protein in environmental enrichment group were increased remarkably,meanwhile,the ratio of LC3-Ⅱ/LC3-Ⅰwas significantly increased(P<0.01).Conclusion:Environmental enrichment intervention can significantly improve the spatial memory ability of HIBD immature rats.The up-regulated expression of BDNF and activation of autophagy signal in hippocampus may be one of the internal mechanisms.