青蒿琥酯对阿尔茨海默症模型大鼠学习记忆的改善作用

Artesunate improve learning and memory functions in Alzheimer's rats

目的:观察青蒿琥酯对阿尔茨海默症(AD)模型大鼠学习记忆的改善作用,并探讨其可能的抗炎机制。方法:雄性SD大鼠分为4组,假手术组(n=8),AD模型组(n=10),AD+青蒿琥酯高剂量组(n=6)和AD+青蒿琥酯低剂量组(n=7),双侧海马CA1区注射β-淀粉样蛋白1-40(Aβ1-40)制备AD模型大鼠,连续14 d腹腔注射青蒿琥酯(80mg/kg和20 mg/kg)。水迷宫实验检测大鼠学习记忆能力; ELISA检测脑内皮质组织IL-6、TNF-α的含量; Western blot检测海马组织GluR2、GluR1蛋白的表达量。结果:与假手术组相比,AD模型组大鼠的水迷宫逃避潜伏期明显延长(P <0. 05);与AD模型组相比,青蒿琥酯高剂量组的逃避潜伏期有所缩短(P <0. 05),且空间探索实验中的原平台穿越次数增加(P <0. 05);而青蒿琥酯低剂量组的平台穿越次数较AD模型组增加(P <0. 05),但其逃避潜伏期与AD模型组无统计学差异。ELISA检测结果显示,AD模型组大鼠的IL-6和TNF-α高于假手术组(P <0. 01),而青蒿琥酯高剂量组和低剂量组均低于AD模型组(P <0. 05)。Western blot结果显示,AD模型组大鼠海马GluR2和GluR1的蛋白表达低于假手术组(P <0. 05),而高剂量青蒿琥酯组高于AD模型组(P <0. 05)。结论:青蒿琥酯对AD模型大鼠的学习记忆可能有一定改善作用,其机制可能与其抗炎、缓解α-氨基-3-羟基-5-甲基-4-异恶唑丙酸(AMPA)受体数量减少作用有关。

AIM: To observe the effects of artesunate on learning and memory functions in rats with Alzheimer’s disease( AD) and then explore the role of inflammation in it. METHODS: Male SD rats were randomly divided into 4 groups, including sham operation( n = 8),AD model( n = 10),AD+ high-dose artesunate( 80 mg/kg,n = 6),and AD + low-dose artesunate( 20 mg/kg,n = 7). By using brain stereotaxic technique,AD model rats were prepared by microinjection of Aβ1-40 into area CA1 of bilateral hippocampus. The rats were injected intraperitoneally with artesunate for 14 consecutive days. The learning and memory functions of rats were evaluated with Morris water maze test. ELISA Kit was used to detect the levels of IL-6 and TNF-αin cortical and western blot assay was used to detect the expression of GluR2 and GluR1 in hippocampus.RESULTS: Morris water maze test showed that the AD group prolonged the escape latency when compared with the sham group,which relieved by highdose artesunate administration( P < 0. 05). The results of ELISA showed that the levels of IL-6 and TNF-α in AD group increased when compared with sham group,which reveserved by artesunate treatment( P < 0. 05). Western blot results showed that the expression of GluR2 and GluR1 protein level in hippocampus of AD group were decreased as compared with sham operation group; artesunate significantly increased GluR2 and GluR1 protein level when compared with AD groups( P < 0. 05). CONCLUSION: Artesunate may have a protective effect on learning function of AD rats,and its mechanism may be related to its anti-inflammatory effects on the reduction of AMPA receptors.