摘要
目的:观察复方中药脑尔康对阿尔茨海默病(Alzheimer's disease,AD)模型大鼠海马β淀粉样肽1-42(β-amyloid peptide1-42,Aβ1-42)及其降解酶——脑啡肽酶(neprilysin,NEP)表达的影响,探讨其抗痴呆的作用机制。方法:48只健康雄性SD大鼠随机分为空白对照组、模型组、吡拉西坦组和大、中、小剂量脑尔康组,每组8只。除空白对照组外,其余各组大鼠双侧海马CA1区各一次性注射凝聚态Aβ1-425μL(2μg/μL)制备AD模型,空白对照组注射等体积生理盐水。3个剂量脑尔康组大鼠给予脑尔康[60、30、15g/(kg·d)]连续灌胃28d,吡拉西坦组给予吡拉西坦[0.375g/(kg·d)]灌胃,空白对照组和模型组给予等量生理盐水灌胃。采用Y型电迷宫检测大鼠学习记忆能力,采用免疫组织化学法检测海马内Aβ1-42和NEP的表达。结果:大鼠海马注射Aβ1-42后,与空白对照组比较,模型组大鼠学习记忆能力下降,海马内Aβ1-42表达明显增多(P<0.01)。用药干预28d后,与模型组比较,吡拉西坦组和各剂量脑尔康组大鼠学习记忆能力改善(P<0.05,P<0.01),海马内Aβ1-42的表达下降(P<0.05,P<0.01),NEP的表达增加(P<0.05,P<0.01),其中以大剂量脑尔康组效果最佳。结论:复方中药脑尔康可能通过上调AD模型大鼠海马NEP的表达来降低Aβ1-42的含量,改善其学习记忆能力,发挥抗痴呆作用。
Objective： To investigate the effects of Naoerkang （NEK）, a compound traditional Chinese herbal medicine, on the expressions of β-amyloid peptide 1-42 （Aβ1-42） and neprilysin （NEP） in hippocampal tissues in a rat model of Alzheimers disease （AD）.
Methods： Forty-eight male SD rats were randomly divided into normal control group, untreated group, piracetam group, low-dose NEK group, medium-dose NEK group, and high-dose NEK group, with 8 rats in each group. Five microliters of Aβ1-42 （2 μg/μL） were injected into CA1 area of hippocampus in rat to establish AD model whereas the normal control rats were injected with same volume of normal saline for comparison. The rats in the NEK groups were treated respectively with high-, medium- and low-dose [60, 30, 15 g/（kg·d）] NEK for 28 days consecutively; piracetam [0.375 g/（kg·d）] was intragastrically administered to rats in the piracetam group; and normal saline was applied in the control and untreated groups. Y-maze test was used for behavioral study to test the learning and memory abilities of rats in different groups. The expressions of Aβ1-42 and NEP in hippocampus were determined by immunohistochemical method, and the results were analyzed by image acquisition and analysis system.
Results： Injection of Aβ1-42 could induce learning and memory dysfunction and up-regulate Aβ1-42 expression in hippocampal tissue in rats of the untreated group. Compared with the normal control group, the abilities of learning and memory of rats in the untreated group were significantly decreased （P〈0.01） and the expression of Aβ1-42 was significantly increased （P〈0.01） after model establishment. After 28-day administration of NEK and piracetam, the abilities of learning and memory of AD rats in piracetam and low-dose, medium-dose and high-dose NEK groups were significantly improved as compared with the untreated group （P〈0.01 or P〈0.05）; the expression of Aβ1-42 in hippocampal tissues was decreased （P〈0.01 or P〈0.05） and the expression of NEP was increased （P〈0.01 or P〈0.05）, especially in the high-dose NEK group.
Conclusion： NEK can play the role of anti-dementia by increasing the expression of NEP in hippocampal tissues of AD rats so as to reduce the quantity of Aβ1-42 and by improving the ability of learning and memory of rats with AD.
出处
《中西医结合学报》
CAS
2010年第2期152-157,共6页
Journal of Chinese Integrative Medicine
基金
陕西省科技攻关计划资助项目[No:2007K16-07(5)]
