蝙蝠葛酚性碱对阿尔茨海默病模型小鼠学习记忆和海马的影响

Effect of Phenolic Alkaloids of Menispermum dauricum on Learning and Memory and Hippocampal in Alzheimer's Disease Model Mouse

目的:探讨蝙蝠葛酚性碱(PAMD)对阿尔茨海默病(AD)模型小鼠学习记忆和海马的影响。方法:C57BL/6小鼠随机分成对照组,模型组,吡拉西坦组(620 mg·kg-1),PAMD高、中、低剂量组(30,15,7.5 mg·kg-1)。采用D-半乳糖(180 mg·kg-1)ip和双侧海马微量注射(10μg)β-淀粉样蛋白1-42(Aβ1-42,2 g·L-1)诱导AD模型小鼠。所有小鼠给予等体积药物或生理盐水ig,持续28 d。采用Morris水迷宫测试行为学指标,观察小鼠学习记忆能力及小鼠海马镜下形态结构,采用双抗体夹心法测定脑组织β-淀粉样蛋白(Aβ)和白介素-6(IL-6)水平。结果:与对照组比较,模型组小鼠潜伏期和游泳距离明显增加(P<0.05),Aβ和IL-6水平明显升高(P<0.05)。与模型组比较,PAMD高、中剂量组明显改善AD模型小鼠的学习记忆能力(P<0.05),明显改善海马神经元的细胞形态,明显降低Aβ和IL-6的水平(P<0.05)。结论:PAMD改善AD模型小鼠的学习记忆功能及海马神经元的形态结构,PAMD通过抑制Aβ和IL-6蛋白在AD治疗中发挥重要作用。

Objective： To explore the effect of phenolic alkaloids of Menispermum dauricum （PAMD） on the learning and memory and hippocampal in Alzheimer＇s disease （AD） model mouse. Method： C57BL/6 mouse were randomly divided into control group, Piracetan group （620 mg·kg^-1）, PAMD high-dose group （30 mg·kg^-1）, PAMD medial-dose group （15 mg·kg^-1）, PAMD low-dose group （7.5 mg·kg^-1）. By using intraperitoneal injection of D-galactose （180 mg ·kg^-1） in combination with microinjection of 10 μg incubated amyloidbeda protein1-42 （Aβl-42, 2 g ·L^-1） into the dorsal blade of the dentale gyrus in the bilateral hippocampus of mouse an AD model mouse was induced. All the mice were ig administrated with drugs or water in the same voume for 28 days. The Morris water maze was used to observe the learning and memory ability. After the treatment all animals were sacrificed, morphology of hippocampus was observed. Biochemical methods were used to determine the content of Aft and interleukin-6 （IL-6） in the brain tissue. Result： Compared with the control group, model group latencies and swimming distances significantly prolonged （P 〈 0.05 ）, Aft and IL-6 significantly increased （P 〈 0. 05） ; compared with the model group, PAMD high-dose group and PAMD medial- dose group could significantly improve the learning and memory ability of model mouse （P 〈 0.05）. In PAMD high-dose group and PAMD medial-dose group, the brain maintain normal morphological structure of nerve cells and the number of nerve cells was significantly increased, Aβ and IL-6 were significantly decreased （P 〈 0.05）. Conclusion： PAMD could improve the ability of learning and memory of AD model mouse. PAMD can maintain normal morphological structure of nerve cells of AD mice. PAMD plays a certain role in the treatment of AD through inhibiting Aβ and IL-6.