芸香苷对慢性脑低灌注大鼠认知功能障碍和脑损伤的神经保护作用

Neuroprotective Effect of Rutin on Cognitive Dysfunction and Brain Injury Induced by Chronic Cerebral Hypoperfusion in Rats

目的:研究芸香苷对慢性脑低灌注导致大鼠认知功能障碍和脑损伤的影响。方法:采用双侧颈总动脉结扎法(bilateral common carotid artery occlusion,BCCAO)建立慢性脑低灌注大鼠模型,随机分为4组(n=10):生理盐水治疗模型组、芸香苷治疗模型组、生理盐水治疗假手术组、芸香苷治疗假手术组;连续腹腔注射芸香苷和生理盐水共12周。采用Morris水迷宫评定大鼠学习和记忆能力。采用分光光度法检测脑组织中枢胆碱能相关指标和氧化应激指标。应用免疫组织化学和El ISA方法检测脑组织炎症反应。采用Nissl染色法检测脑组织神经元缺失。结果:芸香苷治疗模型组大鼠的逃脱潜伏期较生理盐水治疗模型组明显减少(P<0.01)。与生理盐水治疗模型组相比,芸香苷治疗后显著提高了BCCAO大鼠脑组织中ACh水平(P<0.01)和Ch AT活性(P<0.01),并降低了ACh E活性(P<0.01)。与生理盐水治疗模型组相比,芸香苷治疗模型组显著增加了大鼠脑组织中SOD活性(P<0.01)和GPX活性(P<0.01),降低了MDA水平(P<0.01)和蛋白质羰基化合物水平(P<0.01)。芸香苷治疗模型组大鼠海马区GFAP-免疫阳性星型胶质细胞(P<0.01)和Iba1-免疫阳性小胶质细胞(P<0.01)面积百分比较生理盐水治疗模型组显著减少。芸香苷治疗模型组大鼠海马区正常神经元的数量较生理盐水治疗模型组大鼠显著增加(P<0.01)。结论:芸香苷可改善慢性脑低灌注引起的大鼠认知功能障碍和脑损伤。

Objective： To study effect ofrutin on cognitive dysfunction and brain injury in a rat model of chronic cerebral hypop- erfusion. Methods： The bilateral carotid artery ligation （bilateral common carotid artery occlusion and BCCAO） to establish rat model of chronic cerebral hypoperfusion and randomly assigned to 4 groups （n = 10）： sham operation group treated with saline model group, rutin treatment model group, normal saline treatment, rutin treatment in the sham operation group; continuous intraperitoneal injection ofrutin and saline for 12 weeks. Morris water maze was used to evaluate the learning and memory ability of rats. Determination of central cholin- ergic and oxidative stress in brain tissue by spectrophotometry. Detection of inflammatory response in brain tissue by immunohistochem- istry and EIISA method. Detection of neuronal loss in brain tissue by Nissl staining. Results： Escape latency compared to saline treated model group, mtin treatment of rats in the model group were significantly reduced （P〈0.01）. Compared with the saline treated model group, rutin treatment significantly increased the BCCAO rats brain tissue in ACh levels （P〈0.01） and chat activity （P〈0.01）, and de- crease the activity of ache （P〈0.01）. Compared with the saline treated model group, rutin in model group significantly increased the rat brain tissue SOD activity （P〈0.01） and GPX activity （P〈0.01）, decreased the MDA levels （P〈0.01） and protein carbonyl compound levels （P〈0.01）. The Rue glycosides treatment of model group rats hippocampal GFAP immunoreactive satellite glial cells （P〈0.01） and im- mune Ibal positive microglia cells （P〈0.01） area percent compared to saline treated model group decreased significantly. The number of normal rue glycosides treatment of model group rats hippocampus neuron than in physiological saline treatment model group rats was significantly increased （P〈0.01）. Conclusion： Rutin can improve chronic cerebral hypoperfusion in rats induced by cognitive dysfunction and brain damage.