红车轴草素对Aβ诱导大鼠认知障碍的保护作用  

The protective mechanism of pratensein on Beta-amyloid-induced cognitive deficits in Wistar rats

作　　者：聂金兰 谭实美 黄权芳[2] 林兴[1] 

机构地区：[1]广西医科大学,南宁530021 [2]广西中医药大学第一附属医院,南宁530023

出　　处：《中药药理与临床》2016年第3期20-24,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(81260674;81473431);广西自然科学基金(2013GXNSFAA019146)

摘　　要：目的:探讨对β1-42淀粉样蛋白(Aβ1-42)诱导的大鼠认知障碍的保护作用及其机制。方法:10周龄Wistar大鼠随机分成假手术组、Aβ1-42模型组、阳性药(石杉碱甲0.05 mg/kg)对照组、红车轴草素10 mg/kg和20 mg/kg治疗组。采用侧脑室注射Aβ1-42建立大鼠认知障碍模型,治疗3周后,应用Morris水迷宫行为试验测试大鼠的学习记忆能力,利用Western blot法检测大鼠海马中Aβ1-42蛋白、突触可塑性相关蛋白(PSD-95、p-NMDAR1、p-Ca MKII、p-PKACβ、PKCγ、p-CREB)和BDNF蛋白的表达。Realtime PCR分析Aβ相关基因APP、BACE1、Cat B、NEP和IDE mRNA的表达。采用碱性羟胺比色法测定大鼠脑乙酰胆碱酯酶(ACh E)含量。结果:红车轴草素(10 mg/kg、20 mg/kg)可明显改善大鼠学习记忆能力,减轻海马神经元退化和凋亡,提示对Aβ1-42诱导的大鼠认知损伤有明显的改善作用。进一步的机制研究表明红车轴草素可增强PSD-95、p-NMDAR1、p-Ca MKII、p-PKACβ、PKCγ、pCREB和BDNF蛋白的表达;抑制APP、BACE1和Cat B mRNA的表达,但提高NEP和IDE mRNA的水平;降低β淀粉样多肽的含量和沉积;同时,能明显降低脑内胆碱酯酶的活性,增加乙酰胆碱的含量。结论:红车轴草素能改善Aβ1-42诱导的大鼠认知障碍,其作用机制可能与降低脑内Aβ蛋白、增强突触可塑性相关蛋白表达和降低胆碱酯酶的活性有关。Aim： To investigate the protective effect and mechanism of pratensein on the cognitive deficits induced by Aβ1-42 in rats. Methods： Ten-week old Wistar rats were randomly divided into five groups consisting of 15 animals per group, including sham group, Aβ1-42 model group, positive group （0.05 mg/kg huperzine A） , and pratensein-treated groups （ 10 and 20 mg/kg pratensein）. The rats were injected with Aβ1,42 into the bilateral hippoeampus to induce the cognitive impairment model. After a treatment period of 3 weeks, the spatial learning and memory, Aβ1- 42 protein, synapse plasticity related proteins （PSD-95 ,p-NMDAR1 ,p-CaMKⅡ, p-PKACⅡ, PKCγ, p-CREB ）, BDNF protein, as well as the Aβ-related genes （APP, BACE1, CatB, NEP, IDE） were evaluated. And the Aeetylcholinesterase （ACHE） activity was also determined. Results： pratensein （10 mg/kg,20 mg/kg） significantly improved the abilities of learning and memory and ameliorated the rleu- tonal degeneration and apoptosis in hippoeampal, suggesting its protective effect on A^z2-induced cognitive impairment. The mechanism study showed that pratensein treatment resulted in significant increase in the proteins expressions of PSD-95, p-NMDARI, p-CaMKII, p- PKACβ, PKCβ, p-CREB and BDNF, and over-expressions of APP, BACE1 and CatB mRNA, as well as down-regulation of NEP and IDE mRNA. Pratensein markedly decreased the content and deposits of β-amyloid peptides. In addition, Pratensein treatment decreased the activ- ity of cholinesterase, then subsequently elevated the level of aeetylcholine. Condation： Pratensein could improve the cognitive impairment induced by Aβ1-42 in rats, and the mechanism of protection may be related to the decrease in Aβ content and deposition, the improvement of synaptic plasticity, and the inhibition of AChE activity.

关 键 词：红车轴草素 认知障碍 Β淀粉样蛋白 突触可塑性蛋白 胆碱酯酶 

分 类 号：R285.5[医药卫生—中药学]