黄精对血管痴呆模型大鼠认知功能的保护作用及机制的研究

Protective effects and mechanism of polygonatum sibiricum on the cognitive function in VD model rats

目的:探讨黄精水煎剂对血管性痴呆(Vascular Dementia,VD)模型大鼠的影响。方法:Wistar大鼠随机分为造模组和假手术组。造模组采用双侧颈总动脉反复缺血再灌注加腹腔注射硝普钠的方法构建VD大鼠模型,取造模存活大鼠随机分为模型组、黄精低剂量组(15 g·kg^-1·d^-1)和黄精高剂量组(30 g·kg^-1·d^-1)。假手术组仅分离双侧颈总动脉,不阻断血流,注射生理盐水。造模后每天按规定剂量灌胃给药,连续6周,假手术组和模型组给予等量生理盐水。给药结束后,采用Morris水迷宫检测大鼠的空间学习记忆能力,进行神经行为学评分,尼氏染色检测海马神经元损伤,分光光度法检测海马组织谷氨酸(Glu)和Ca2+含量。结果:Morris水迷宫结果显示,模型组大鼠在定位航行实验中,逃避距离(Escape Distance,ED)与假手术组相比明显延长(P<0.01),在空间探索实验中,目标象限游泳距离与穿越站台次数明显减少(P<0.01);黄精低、高剂量干预治疗后,大鼠的ED明显缩短,目标象限游泳距离与穿越站台次数明显增多,差异有统计学意义(P<0.01,P<0.05)。神经行为学评分结果显示,与假手术组相比,模型组大鼠神经行为学评分明显升高(P<0.01),黄精低、高剂量组的神经行为学评分较模型组明显降低(P<0.01,P<0.05)。尼氏染色显示模型组大鼠海马CA1区尼氏体阳性神经元数目较假手术组明显减少(P<0.01),与模型组相比,黄精低、高剂量组尼氏体阳性神经元数目明显增多(P<0.01)。分光光度法检测结果显示,模型组大鼠海马组织中的Glu和Ca2+含量较假手术组显著升高(P<0.01),黄精低、高剂量组海马中Glu和Ca2+的表达较模型组明显降低(P<0.01)。结论:黄精水煎剂对VD大鼠的空间学习记忆能力和神经行为学损伤有一定程度的保护作用,其机制可能与其降低海马组织中Glu含量,减少海马神经细胞Ca2+超载,从而减轻Glu过度激活诱导的兴奋性神经毒性有关。

Objective:To investigate the protective effects and mechanism of polygonatum sibiricum on vascular dementia model rats.Methods:Adult Wistar rats were randomly divided into the sham operation group and the model group.The survival rats were randomly divided into the model group,low-dose drug group,high-dose drug group.Meanwhile in the sham operation group,bilateral common carotid arteries were isolated without blocking,and normal saline was injected.The rats were daily treated by intragastric administration of low doses and high doses of polygonatum sibiricum for 6 weeks.Meantime,the sham operation group and the model group were given the same amount of normal saline.After the treatment,the spatial learning and memory was examined by Morris Water Maze test with the neurobehavioral scores.And the damage of hippocampal neurons was detected by Nissl staining.Then,the expression of Glu and Ca2+in the hippocampus was detected by spectrophotometry.Results:Morris Water Maze test results revealed that in the model rats escape distance was prolonged more in positioning navigation experiment,and the distance of staying in quadrant of platform and the number of crossing over a platform were fewer than the sham operation group in spatial probe test(P<0.01).However,ED was significantly decreased and the distances of staying in quadrant of platform and the number of crossing over a platform was remarkably longer(P<0.05,P<0.01)in the low-dose drug group and high-dose drug group than the model rats.Compared with the sham operation group,the neurobehavioral scores were significantly increased in the model rats(P<0.01),while those in the high-dose drug group and lowdose drug group was significantly reduced after treatment(P<0.05,P<0.01).Positive neurons of hippocampus was decreased significantly in the model group(P<0.01)and increased in the low-dose drug group and high-dose drug group(P<0.01).The spectrophotometry results showed that the expressions of Glu and Ca2+were significantly increased in the model rats than the sham operation group(P<0.01),whereas remarkably decreased in the low-dose drug group and high-dose drug group than the model rats(P<0.01).Conclusion:Polygonatum sibiricum could improve the ability of spatial learning and memory and the neurobehavioral scores in VD model rats,which may be closely related to regulating the content of Glu and Ca2+in hippocampus,thereby reducing the excited toxicity induced by Glu over-activation.