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目的:研究半夏总生物碱(TAPT)对D-半乳糖诱导的衰老小鼠学习记忆的影响并初步探讨其作用机制。方法:昆明种小鼠100只,随机分为5组,即正常对照组,模型组,TAPT低、中、高剂量组(7.5,15,30 mg.kg-1),每组20只。模型组和TAPT组给予120 mg.kg-1的D-半乳糖注射液(sc,每天1次,连续8周),建立学习记忆障碍的衰老小鼠模型,对照组给予等量生理盐水;同时,TAPT各组给予对应浓度的TAPT药液(ig,每天1次,连续8周),对照组及模型组给予等量蒸馏水。采用跳台法和Y迷宫评价法测试TAPT对模型小鼠学习记忆障碍的改善作用,采用比色法测定小鼠脑组织中丙二醛(MDA)的含量,超氧化物歧化酶(SOD)和乙酰胆碱酯酶(AChE)的活性。结果:TAPT低、中、高剂量组小鼠Y迷宫训练时达标所需总次数减少,分别为(21.9±2.9),(20.8±3.2),(19.7±2.8)次;Y迷宫记忆测试时错误次数也明显减少,分别为(3.8±1.4),(3.2±1.7),(1.7±1.1)次;模型组小鼠脑组织SOD活性明显降低(28.98±13.08)U.mg-1,MDA及AChE含量明显增加(2.78±0.21)nmol.mg-1,(1.05±0.16)U.mg-1;经TAPT干预后,各剂量组小鼠脑组织中SOD活性增高(P<0.01),MDA含量明显降低(P<0.01);中、高剂量组AChE含量显著减少(P<0.01,P<0.05)。结论:应用TAPT干预D-半乳糖诱导的衰老小鼠,可明显改善其学习和记忆功能,这可能与其具有抗氧化作用及抑制AChE的活性有关。
Objective: To study the effect of total alkaloids from Pinellia ternata (TAPT) on learning and memory in aging mice induced by D-galactose and to explore its mechanism. Methods: 100 Kunming mice were randomly divided into 5 groups: normal control group, model group, TAPT low, medium and high dose groups (7.5, 15, 30 mg.kg-1), 20 in each group. The model group and the TAPT group were given 120 mg.kg-1 D-galactose injection (sc, once a day for 8 weeks) to establish an aging mouse model of learning and memory impairment, while the control group was given the same amount of saline; meanwhile, The TAPT groups were given the corresponding concentrations of TAPT solution (ig, once a day for 8 weeks), and the control group and model group were given the same amount of distilled water. The effect of TAPT on the learning and memory impairment of model mice was tested by the method of jumping and Y maze evaluation. The contents of malondialdehyde (MDA), superoxide dismutase (SOD) and acetylcholine Esterase (AChE) activity. Results: The total number of time required for Y maze training in TAPT low, medium and high dose groups was (21.9 ± 2.9), (20.8 ± 3.2) and (19.7 ± 2.8) times, respectively; errors in Y maze test (3.8 ± 1.4), (3.2 ± 1.7) and (1.7 ± 1.1) times, respectively. The activity of SOD in the model group was significantly decreased (28.98 ± 13.08) U.mg-1, MDA and AChE (2.78 ± 0.21) nmol.mg-1 and (1.05 ± 0.16) U.mg-1, respectively. After TAPT intervention, the SOD activity in brain tissue of each dose group increased (P <0.01) (P <0.01). The levels of AChE in medium and high dose groups were significantly decreased (P <0.01, P <0.05). Conclusion: TAPT can significantly improve the learning and memory function of aging mice induced by D-galactose, which may be related to its anti-oxidation and anti-AChE activity.