白藜芦醇甙对缺氧缺血性脑损伤新生大鼠学习记忆和海马突触素表达的影响

Effects of polydatin on learning memory and the expression of synaptophysin in hippocampus induced by hypoxic-ischemic brain injury in neonatal rats

目的探讨白藜芦醇甙（PD）对缺氧缺血性脑损伤（HIBD）新生大鼠空间学习记忆的影响及海马CA1区突触素表达的变化。方法7日龄SD大鼠37只随机分为假手术组、HIBD自然恢复组和PD治疗组，采用经典的Rice方法制备缺氧缺血性脑损伤动物模型，分别在生后28d（缺氧缺血后21d）进行Morris水迷宫测试，评价其学习记忆能力，用免疫组织化学方法来观察各组大鼠海马CA1区突触素的变化。结果HIBD后3周Morris测验，假手术组、HIBD自然恢复组和PD治疗组大鼠4d的平均逃避潜伏期分别为（39．55±8．08）s、（52．37±8．03）s、（43．29±7．63）s，PD治疗组大鼠逃避潜伏期明显短于HIBD自然恢复组（P〈0．05），且3组大鼠在4d内的逃避潜伏期均逐渐变短；3组大鼠穿过平台次数分别为（5．29±2．62）次、（2．36±I．80）次、（4．25±1．66）次，PD治疗组大鼠穿过平台次数显著多于HIBD自然恢复组（P〈0．05）；3组大鼠在目标象限内游泳时间分别为（15．74±3．85）s、（10．63±3．66）s、（14．32±2．52）s，PD治疗组在目标象限内游泳时间明显多于HIBD自然恢复组（P〈0．05）。3组大鼠海马CA1区突触素的平均密度值分别为0．1674±0．0111、0．2612±0．0323和0．2952±0．0443，PD治疗组大鼠海马CA1区突触素表达明显多于HIBD自然恢复组（P〈0．05）。结论白藜芦醇甙能减轻新生大鼠缺氧缺血引起的脑损伤，提高新生大鼠缺氧缺血后远期的学习记忆能力。这种保护作用与白藜芦醇甙能促进HIBD后神经元重塑的突触素表达有关。

Objective To explore the protective effects and possible mechanisms of Polydatin （PD） on hypoxic-ischemia brain injury（HIBD） in neonatal rat by means of spatial learning memory and the ex- pression of synaptophysin in hippocampal CA1. Methods Thirty-seven neonatal SD rats were divided into 3 groups at random：normal sham-operated group（no hypoxia and ischemia） ;HIBD group（ no medication） ;PD treatment group. 7-old-day rat＇ s model of HIBD was established by left carotid artery ligation and 2 h hypoxi- a. Morris water maze test was used to evaluate cognitive function in the rats after 28-day-old（ 21-day later after HI）. Immunohistochemical method was used to measure the expression of synaptophysin after the end of Morris water maze test. Results Morris water maze results showed that the mean escape latency of the sham group （SG） ,HIBD group （HIBD） and PD treatment group （PD） were （39. 55 ±8. 08） s, （52. 37 ±8.03） s and （43.29 ± 7. 63 ） s respectirely. For PD and SG, the mean escape latency was significantly shorter than the HIBD （ P 〈 0. 05 ）. After training, the mean escape latency in the three groups of rats was shortened gradually. The frequency of platform crossings were 5.29 ± 2. 62,2.36 ± 1.80,4. 25 ±1.66 in the SG, HIBD and PD respectirely. The frequency of platform crossings in PD was higher than that of HIBD （ P 〈 0. 05 ）. The swimruing time in target quadrant were （ 15.74 ±3. 85） s, （ 10.63 ±3.66） s and （ 14. 32 ±2. 52） s in SG,HIBD and PD respectirely. For HIBD, the swimming time in target quadrant was significantly shorter comparing to SG and PD （ P 〈 0. 05 ）. The expression of synaptophys in hippocampal CA1 in PD （ 0. 295 2± 0. 044 3） were evidently higher than that in the HIBD group （ 0. 261 2± 0. 032 3 ） at 3 week after operation （ P 〈 0. 05）. Conclusion Spatial learning memory deficits and the decrease of synaptophys in hippocampal CA1 could be induced by hypoxic-ischemia. Polydatin could improve the learning and memory ability in neonatal rats following hypoxic-ischemia brain damage. The mechanisms of improvement with Polydatin treatment is associated with the enhancement of expression of synaptophys.