大黄酚脂质体对阿尔采末病模型小鼠学习记忆的改善作用

目的研究大黄酚脂质体对β-淀粉样肽(Aβ25-35)致阿尔采末病(Alzheimer’s disease,AD)模型小鼠学习记忆障碍的影响,及脑组织超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性的变化。方法小鼠1次性脑室内注射凝聚态Aβ25-353μl(1.0 mmol.L-1)制造AD小鼠模型,然后尾静脉注射相应药物或溶剂,采用Y型迷宫法和跳台法测试大黄酚脂质体对小鼠学习记忆的影响,采用比色法测定小鼠脑组织SOD和CAT活性。结果脑室1次性注射3μl Aβ25-35溶液可引起小鼠学习记忆障碍,同时使脑组织SOD和CAT活性降低;而大黄酚脂质体制剂可不同程度改善Aβ25-35造成的学习记忆障碍,提高脑组织SOD和CAT活性,延长小鼠断头耐缺氧的生存时间。结论大黄酚脂质体制剂对Aβ25-35致AD小鼠记忆障碍有保护作用,其作用机制可能与增强抗氧化酶CAT和SOD活性,提高脑组织对氧自由基的清除能力有关。大黄酚脂质体有望成为治疗AD疾病临床应用的新剂型。

Effects of chrysophanol liposomes on learning and memory in AD model mice

Aim To study the effect of chrysophanol liposomes on learning and memory impairment in mice with Alzheimer′s disease(AD) induced by β-amyloid peptide fragment 25-35(Aβ25-35),and changes in the activity of superoxide dismutase(SOD) and catalase(CAT) in brain tissue in AD model mice.Methods One-time intraventricular injection of condensed matter Aβ25-35 3 μl(1.0 mmol·L-1) was applied to create the AD mice model,and then tail intravenous injection of the drug or solvent was performed.Y-maze and step down tests were used to observe the effects of chrysophanol liposomes on learning and memory in mice.Colorimetric determination was employed to test CAT and SOD activity in mice brain.Results One-time intraventricular injection of 3 μl solution Aβ25-35 could induce learning and memory impairment in mice,and also CAT and SOD in brain tissue.While chrysophanol liposome could improve learning and memory impairment caused by Aβ25-35 in varying degrees,it also could improve SOD and CAT activities in brain tissue and extend the survival time of decapitated mice in hypoxia tolerance.Conclusions Chrysophanol liposome shows protective effects on learning and memory impairment in AD mice induced by Aβ25-35.The mechanism may be through enhancing antioxidant enzymes CAT and SOD activity,raising brain tissue’s ability of scavenging oxygen free radicals.The chrysophanol liposomes are expected to become the new formulations for the treatment of AD disease in clinical applications.