肉苁蓉多糖对东莨菪碱所致学习记忆障碍模型小鼠在突触可塑性方面的保护作用

摘要

目的：研究肉苁蓉多糖( CDPS)对东莨菪碱所致学习记忆障碍小鼠在突触可塑性方面的改善作用。方法昆明小鼠随机分为6组,分别为东莨菪碱模型组、正常对照组、CDPS小剂量(25 mg·kg-1)组、CDPS中剂量(50 mg·kg-1)组、CDPS大剂量(100 mg·kg-1)组和阳性对照组。除正常对照组外,其他组小鼠口服给CDPS 6周,并于Morris水迷宫训练第4天前腹腔注射东莨菪碱4mg·kg-1,30 min后进行行为学指标测定,包括Morris水迷宫和跳台试验。处死取脑海马组织,运用Western blot技术及RT-PCR比较小鼠海马区GAP-43, SYP以及PSD-95的蛋白水平及基因水平的表达差异,并用透射电镜观察海马CA3区突触数量与相关结构的变化。结果 CDPS (25、50、100 mg·kg-1)组小鼠与正常对照组小鼠在水迷宫实验的潜伏期明显短于模型组小鼠,而且在Q3象限的时间明显大于模型组小鼠。 CDPS (50、100 mg·kg-1)组小鼠跳台实验中的错误次数与模型组小鼠相比减少。 Western blot与RT-PCR实验结果显示,模型组小鼠海马区GAP-43、SYP的表达水平与正常对照组比较明显降低。 CDPS (25、50、100 mg·kg-1)组小鼠海马区SYP的表达较模型组明显增高,CDPS (25、50 mg · kg-1)组小鼠海马区GAP-43的表达水平较模型组明显增高,PSD-95的表达在不同组中没有明显变化。最后,我们观察小鼠海马CA3区的超薄切片发现,CDPS可以使CA3区突触数量增多。结论东莨菪碱可以造成小鼠学习记忆障碍模型,并使小鼠海马区相关蛋白表达异常,由此引起突触可塑性的变化,进而导致学习记忆能力的改变。而CDPS能够提高SYP与GAP-43的表达,增多突触数量,使突触可塑性有所恢复,并且改善小鼠的学习记忆能力。%Aim To investigate the effect of polysac-charide of Cistanche deserticola ( CDPS) on the impro-ving ability of synaptic plasticity in memory acquisition impairment model mice induced by scopolamine. Methods The KM mice were randomly divided into six groups:scopolamine group, control group, CDPS-treated (25, 50, 100 mg·kg-1 ) group and donepezil group. Memory acquisition impairment model in mice was established with i. p. scopolamine (4 mg·kg-1 ) only once, and orally administered CDPS (25, 50, or 100 mg · kg-1 ) daily for 6 weeks before scopolamine injection. Experimental groups were subjected to step-down test and Morris water maze test. Western blot and RT-PCR analysis were used to examine the expression of GAP-43 , SYP and PSD-95 . Transmission electron microscope was used to observe the change of synaptic number and structures. Results CDPS (25,50,100 mg·kg-1 ) could shorten the incubation period of mice in the water maze test. Control group and CDPS-treated group swam longer in Q3 than scopolamine group. Mo-reover, CDPS (50,100 mg·kg-1 ) could significantly reduce the error times and extend the incubation period in the step-down test. The results of Western blot and RT-PCR showed that CDPS significantly improved the expression of GAP-43 at the dose of 25 ,50 mg · kg-1 and SYP at the dose of 25,50, 100 mg·kg-1 in hip-pocampus of mice. However, the biochemical assays did not reveal a significant difference in the basal hipp-ocampal levels of the PSD-95 . The ultra-thin speci-mens of hippocampus showed that the number of syn- apse was increased in CDPS-treated group. Conclu-sions Scopolamine can induce the learning and mem-ory deficits in mice to make related protein expression abnormalities in hippocampus mice, thus this causes the change of synaptic plasticity, which leads to a change in the ability of learning and memory. And CDPS can improve the expression of SYP and GAP-43 , increase number of synapses, recover synaptic plastici-ty, and improve the ability of learning and memory in mice.