麋角丸改善Aβ_(1-42)海马区注射小鼠学习与记忆能力的作用机制研究

Exploration of the Mechanism of Mijiao Pill in Improving the Learning and Memory Ability of Aβ_(1-42) Hippocampus Injection Mice

目的评价麋角丸对Aβ_(1-42)海马区注射小鼠学习与记忆能力的改善作用与作用机制研究。方法采用海马区注射β淀粉样多肽1-42(Aβ_(1-42))构建拟阿尔茨海默症(AD)小鼠模型,给以麋角丸提取物。通过Morris水迷宫实验检测小鼠的学习与记忆能力,尼氏染色法检测海马DG区神经元损伤程度,酶联免疫吸附法检测小鼠海马组织中炎症因子表达,试剂盒检测氧化应激因子表达,蛋白质印迹法检测小鼠海马区中氧化应激与凋亡相关蛋白表达。结果麋角丸显著缩短模型小鼠上台潜伏期和上台前路程,增加穿越站台次数。同时,麋角丸给药显著增加海马DG区尼氏体数量,并下调模型小鼠海马组织中炎症因子的表达,提升SOD活力,降低LDH活力和MDA表达,提高Nrf2、HO-1蛋白表达与Bcl-2/Bax比值,下调Caspase-3、Caspase-9凋亡通路蛋白表达。结论麋角丸具有改善Aβ_(1-42)海马区注射小鼠学习与记忆能力的效用,其作用途径与抑制中枢氧化应激与炎性损伤导致的神经元损伤有关。Nrf2/HO-1通路是其抗海马组织氧化损伤调控信号通路。

Objective To evaluate the effect and mechanism of Mijiao Pill on learning and memory ability of Aβ_(1-42) hippocamps injection mice.Methods A mice model of Alzheimer's disease(AD)was established by injectingβ-amyloid polypeptide 1-42(Aβ_(1-42))into hippocampus.Mice were treated with Mijiao Pill extracts.Morris water maze were used to evaluate the learning and memory ability of mice.Nissl staining was used to detect the degre of neuronal injury in DG area of hippocampus.The expressions of inflammatory cytokines in hippocampus of mice were detected by ELISA method.The expressions of oxidative stress factors were detected by related kits,and the expressions of oxidative stress and apoptotic related proteins in the hippocampus of mice were detected by Western blotting.Results Mijiao Pill significantly shortened the incubation period on stage and the distance before going on stage,and increased the times of crossing the platform.At the same time,Mijiao Pill significantly increased the number of Nissl bodies in DG area of hippocampus,down regulated the expression of inflammatory factors in hippocampus of model mice,increased SOD activity,decreased LDH activity and MDA expression,increased the expression of Nrf2,HO-1 protein and Bcl-2/Bax ratio,and down regulated the expression of caspase-3 and caspase-9 apoptosis pathway protein.Conclusion Mijiao Pill has the effect of improving Aβ_(1-42) hippocampal injection on learning and memory in mice,which is related to the inhibition of neuronal damage caused by central oxidative stress and inflammatory injury.Nrf2/HO-1 pathway is its regulatory signal pathway against oxidative damage in hippocampus.