β-细辛醚对Aβ_(1-42)联合2-VO致AD大鼠的保护作用及机制初探  

Protective effect of β-asarone on AD rat model induced by intracerebroventricular injection of Aβ_(1-42) combined 2-VO and its mechanism

作　　者：王博林 宣玲 戴世杰[1] 姬丽婷 李昌煜[1] 杨元宵[2] 

机构地区：[1]浙江中医药大学药学院,浙江杭州310053 [2]杭州医学院基础医学部,浙江杭州310053

出　　处：《中国中药杂志》2017年第24期4847-4854,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81403128);浙江省医药卫生科技计划项目(2015KYA062)

摘　　要：该文通过侧脑室注射Aβ_(1-42)联合2-VO建立AD大鼠模型,探究β-细辛醚对该模型学习记忆障碍的保护作用,并初步探讨其作用机制。将105只大鼠随机分为7组,分别为假手术组、AD模型组、β-细辛醚低、中、高剂量组(10,20,30 mg·kg^(-1))、多奈哌齐组(0.75 mg·kg^(-1))和银杏叶提取物组(24 mg·kg^(-1)),不同药物给药4周后检测大鼠学习记忆能力、局部脑血流量变化、海马CA1区病理改变、皮质HIF-1α水平及血清CAT,SOD和MDA水平。结果显示,侧脑室注射Aβ1-42联合2-VO导致大鼠学习记忆障碍,局部脑血流量降低,CA1区神经元排列紊乱、出现大量空泡、淀粉样沉淀增多,皮质HIF-1α阳性细胞数显著增加,血清CAT和SOD显著下降,MDA显著上升。给予20,30 mg·kg^(-1)β-细辛醚后,上述症状均得到显著改善。结果表明,β-细辛醚能够缓解Aβ_(1-42)联合2-VO建立AD大鼠模型的症状,其作用机制可能是β-细辛醚通过提高机体抗氧化能力,降低体内的活性氧类物质,从而降低HIF-1α水平,减轻了过氧化物及HIF-1α对神经细胞的损伤,最终达到缓解AD的目的。This study was aimed to investigate the protective effect and mechanism of β-asarone on the animal model of Alzheimer＇s disease（AD） which was induced by intracerebroventricular injection of Aβ1-42 combined cerebral ischemia. One hundred and five rats were randomly divided into seven groups including sham-operated group, AD model group, β-asarone 10 mg·kg^-1 group, β-asarone 20 mg·kg^-1group, β-asarone 30 mg·kg^-1 group, donepezil group（0.75 mg·kg^-1） and Ginkgo biloba extract group（24 mg·kg^-1）. Rats＇ learning and memory abilities, cerebric regional blood flow, pathological changes in hippocampal CA1 region, the expression level of HIF-1α and serum CAT, SOD and MDA level were detected 4 weeks later. The results showed that the application of intracerebroventricular injection of Aβ1-42 joint 2-VO could lead to rats＇ dysfunction of learning and memory, decrease in regional cerebral blood flow. Neurons in CA1 region were arranged in disorder, and amyloid deposition was increased. The number of cerebral cortical cells expressing HIF-1α was increased as well. The level of serum CAT and SOD decreased, while level of serum MDA increased. However these symptoms were improved by 20 mg·kg^-1 and 30 mg·kg^-1β-asarone. The results indicated that β-asarone could effectively relieve the symptoms of the AD model induced by intracerebroventricular injection of Aβ1-42 combined cerebral ischemia, and the potential mechanism might be that it could attenuate damage of MDA to the body by improving the level of CAT and SOD, meanwhile the level of HIF-1α decreased as the decline of hyperoxide which might attenuate its damage to neuron, so it finally achieved alleviating Alzheimer＇s disease.

关 键 词：Β-细辛醚 阿尔茨海默 AΒ1-42 双侧颈总动脉结扎术 抗氧化酶 HIF-1α 

分 类 号：R285.5[医药卫生—中药学]