桃叶鸦葱总黄酮对脑缺血再灌注大鼠海马区Aβ与APP表达的影响

Effect of Total Flavonoids from Scorzonera Sinensis Lipsch on Expression of Hippocampal Amyloid-beta and Amyloid Precursor Protein in Rats After Cerebral Ischemia-Reperfusion

【目的】探讨桃叶鸦葱总黄酮对脑缺血再灌注大鼠海马区β淀粉样蛋白(Aβ)及其前体(APP)表达的影响。【方法】将60只SD大鼠随机分成假手术组,模型组,桃叶鸦葱总黄酮高、中、低剂量组(灌胃剂量分别为400、200、100 mg·kg^(-1)·d^(-1)),尼莫地平组(灌胃剂量为10.8 mg·kg-1·d-1),每组10只。将模型组和各给药组大鼠采用大脑中动脉线栓法制备脑缺血再灌注损伤模型。造模后24 h,观察各组大鼠神经行为学表现并进行评分,采用免疫组织化学法检测各组大鼠海马区Aβ42与APP的表达。【结果】模型组大鼠均表现出明显的神经功能缺损症状,神经行为学评分较假手术组显著升高(P<0.01),而桃叶鸦葱总黄酮高、中剂量组及尼莫地平组大鼠神经功能缺损症状较模型组明显改善,神经行为学评分显著降低(P<0.05)。免疫组织化学结果显示,模型组大鼠Aβ42和APP表达水平显著高于假手术组(P<0.01),而桃叶鸦葱总黄酮高、中剂量组及尼莫地平组大鼠Aβ42和APP表达水平显著低于模型组(P<0.05或P<0.01)。【结论】在脑缺血再灌注损伤过程中,阿尔茨海默病的特征性蛋白Aβ42和APP表达增加,而桃叶鸦葱总黄酮可降低Aβ和APP蛋白的表达水平,具有神经保护作用。

Objective To explore the effect of total flavonoids from Scorzonera Sinensis Lipsch（TFSSL）on theexpression of hippocampal amyloid beta protein（Aβ）and amyloid precursor protein（APP）in rats after cerebralischemia-reperfusion. Methods Sixty rats were randomly divided into 6 groups,namely sham-operation group,model group,nimodipine group（10.8 mg·kg^-1·d^-1,i.g.）,and high-,middle-,and low-dose TFSSL groups（400,200,100 mg·kg^-1·d^-1 respectively,i.g.）,10 rats in each group. The rat model of cerebral ischemiareperfusion was established by middle cerebral artery occlusion（MCAO）-reperfusion method. Twenty-four hoursafter modeling, the neurobehavioral performance of rats in various groups was observed and neurobehavioralscoring was carried out. The expression levels of Aβ42 and APP in hippocampus of rats were detected byimmunohistochemistry. Results The obvious symptoms of nerve function defect were seen and the neurobehavioralscores were increased in the model group as compared with those in the sham-operation group（P〈0.01）.Compared with those in the model group, the symptoms of nerve function defect were improved and theneurobehavioral scores were decreased in high-and middle-dose TFSSL groups and nimodipine group（P〈0.05）.Immunohistochemistrical results showed that the expression levels of Aβ42 and APP in the model group weresignificantly higher than those of the sham-operation group（P〈0.01）,while the expression levels of Aβ42 andAPP in high-and middle-dose TFSSL groups and nimodipine group were significantly lower than those in themodel group（P〈0.05 or P〈0.01）. Conclusion During the course of MCAO injury,the expression levels of Aβ42 and APP as characterized proteins for Alzheimer disease were increased, while TFSSL can decrease theirexpression levels,and have neuro-protective effect.