白藜芦醇对脑出血大鼠运动能力改善和抗神经炎症影响的研究

发布时间：2018-08-17 13:06

【摘要】：研究目的:观察天然抗氧化剂白藜芦醇对脑出血模型大鼠继发性脑损伤的神经保护作用,并探讨其发挥神经保护作用的分子生物学影响。研究方法:SD雄性大鼠随机分组:假手术组、脑出血组和白藜芦醇组。所有实验模型大鼠每天均在同一时间段腹腔给药一次,并分别利用行为学检测方法疲劳转棒实验和旷场实验检测大鼠在造模前和造模后的运动能力变化,以评估其运动能力的恢复情况。在一系列行为学检测完毕之后,模型大鼠被统一处死,取大脑半球标本并固定。海马区神经元损伤及神经细胞凋亡情况用尼氏染色方法检测。用免疫荧光染色法标记Iba-1检测大脑皮质区脑组织小胶质细胞激活情况。并在高倍荧光倒置显微镜下进行组织形态学观察,用高清数码相机拍摄观察区域作后期数据定量分析。所有数据用统计学软件进行统计分析并制作图表。结果:白藜芦醇组大鼠在行为学实验中表现要显著强于脑出血组大鼠,且在2周左右差异最为明显。在疲劳转棒实验中,脑出血组与白藜芦醇组大鼠的运动能力在术后1天没有明显差异。从术后1周开始,白藜芦醇组大鼠运动能力开始逐渐恢复,而脑出血大鼠则是2周之后才开始出现运动能力恢复的迹象。白藜芦醇组大鼠在给药2周后相比脑出血组大鼠有显著差异。在旷场实验中,脑出血组和白藜芦醇组大鼠的运动距离,平均速度以及旋转次数三项指标,相比于假手术组大鼠在术后1天检测时均明显下降。但在给药1周后,白藜芦醇组大鼠的运动距离和平均速度两项指标相比于脑出血组大鼠有明显的差异,从一定程度上体现了白藜芦醇组大鼠的运动能力恢复情况。在尼氏染色结果中发现,大鼠海马区脑组织的神经元数量在造模之后显著下降,但在给药后,海马区脑组织的神经损伤明显减轻,存活的神经元数量相比脑出血组大鼠有显著差异。在小胶质细胞免疫荧光的结果中发现,脑出血组和白藜芦醇组大鼠在造模成功后,小胶质细胞被大量激活,引起强烈的神经炎症反应。而给药之后的大鼠其小胶质细胞激活数显著降低,大鼠脑出血继发性脑损伤引起的炎症反应得到一定程度的缓解。结论:本研究结果表明白藜芦醇可以明显促进脑出血大鼠脑损伤后运动能力的恢复,减少血肿所致的海马区尼氏小体数量的减少和神经元损伤。白藜芦醇也可以通过减少小胶质细胞的激活,起到抗神经炎症反应的效果,从而有效地缓解脑出血后继发性脑损伤。意义:研究白藜芦醇对脑出血大鼠运动能力和神经功能损伤的影响,进一步验证可能的生物学调控作用,进而为下一步毒理学、临床预实验以及可能的药物开发方向提供实验理论基础。
[Abstract]:Aim: to observe the neuroprotective effect of resveratrol on secondary brain injury in rats with cerebral hemorrhage and to explore the molecular biological effects of resveratrol on neuroprotection. Methods male SD rats were randomly divided into three groups: sham operation group, intracerebral hemorrhage group and resveratrol group. All the experimental model rats were administered intraperitoneally every day at the same time, and the changes of motor ability of rats before and after modeling were measured by using behavioral test method, fatigue rotation test and open field experiment respectively. To assess the recovery of its athletic ability. After a series of behavioral tests were completed, the model rats were uniformly killed, the hemispheric specimens were taken and fixed. Neuronal injury and neuronal apoptosis in hippocampus were detected by Nissl staining. The activation of microglia in cerebral cortex was detected by immunofluorescence labeling Iba-1. The histomorphology was observed under high power fluorescence inverted microscope, and the quantitative analysis of the later data was made by using high-definition digital camera. All data are analyzed by statistical software and charts are made. Results: the behavior of resveratrol group was significantly stronger than that of intracerebral hemorrhage group, and the most obvious difference was about 2 weeks. There was no significant difference in motor ability between intracerebral hemorrhage group and resveratrol group 1 day after operation. From 1 week after operation, the motor ability of resveratrol group began to recover gradually, while that of intracerebral hemorrhage rats showed signs of recovery only after 2 weeks. Resveratrol group had significant difference compared with intracerebral hemorrhage group 2 weeks after administration. In the open field experiment, the movement distance, average speed and rotation times of rats in intracerebral hemorrhage group and resveratrol group were significantly lower than those in sham operation group. But after one week of administration, the two indexes of movement distance and average speed in resveratrol group were significantly different from those in intracerebral hemorrhage group, which reflected the recovery of motor ability in resveratrol group to some extent. The results of Nissl staining showed that the number of neurons in rat hippocampal brain tissue decreased significantly after the model was made, but the neuronal damage in hippocampal brain tissue was significantly alleviated after administration of the drug. The number of surviving neurons was significantly different from that of ICH rats. The results of microglia immunofluorescence showed that the microglial cells were activated in large quantities after the successful establishment of the model in intracerebral hemorrhage group and resveratrol group, which caused a strong neuroinflammatory reaction. However, the activation of microglia in rats was significantly decreased after administration of the drug, and the inflammatory response induced by secondary cerebral injury in rats with intracerebral hemorrhage was alleviated to a certain extent. Conclusion: resveratrol can significantly promote the recovery of motor ability and decrease the number of Nissl corpuscles and neuronal damage induced by intracerebral hemorrhage in rats with intracerebral hemorrhage. Resveratrol can also reduce the activation of microglia, play an anti-inflammatory effect, so as to effectively alleviate the secondary brain injury after intracerebral hemorrhage. Significance: to study the effects of resveratrol on motor ability and nerve function injury in rats with intracerebral hemorrhage. Clinical pre-trial and possible drug development provide experimental theoretical basis.
【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R743.34

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