目的 研究开心散对阿尔茨海默症（Alzheimer’s disease，AD）动物模型淀粉样前体蛋白/早老素基因1（amyloid precursor protein/presenilin 1，APP/PS1）双转基因小鼠的作用。方法 将3月龄雄性APP/PS1小鼠随机分为模型组、美金刚（3.33 mg/kg）组及开心散低、中、高剂量（0.33、1.00、3.00 g/kg）组，采用同月龄相同遗传背景C57BL/6J小鼠作为对照组和对照给药（开心散1.00 g/kg）组，每组8只。连续ig给药2个月后，Morris水迷宫实验评价小鼠学习记忆能力；苏木素-伊红（HE）染色法观察小鼠海马CA1区神经元形态；刚果红染色法检测小鼠脑组织淀粉样斑块表达；免疫组化学法检测小鼠皮层和海马中β淀粉样蛋白1-40（amyloid β protein 1-40，Aβ_1-40）、胶质纤维酸性蛋白（glial fibrillary acidic protein，GFAP）和离子钙接头结合调节分子-1（ionized calcium binding adaptor molecule-1，Iba-1）的表达；ELISA法检测小鼠血清中炎症因子肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）和IL-6水平以及皮层和海马中乙酰胆碱（acetylcholine，Ach）水平。结果 与模型组相比，美金刚组和开心散组小鼠学习记忆能力明显提高（P<0.05、0.01），海马CA1区神经元数量增加（P<0.01）；皮层和海马中的淀粉样斑块、Aβ_1-40、GFAP和Iba-1表达明显减少（P<0.05、0.01）；血清中TNF-α、IL-1β和IL-6水平明显降低（P<0.05、0.01）；皮层中Ach水平显著升高（P<0.01）。结论 开心散可能通过抑制星形胶质细胞和小胶质细胞活化，降低血清中炎症因子TNF-α、IL-6、IL-1β水平，减少Aβ和淀粉样斑块的生成，增加皮层中Ach含量，从而发挥保护神经元、防治AD的作用。

Objective To study the pharmacological effects of Kaixin San (开心散) on Alzheimer's disease (AD) aninal model, amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice. Methods Three-month-old male APP/PS1 mice were randomly divided into model group, memantine group (3.33 mg/kg), low-, medium- and high-dose Kaixin San (0.33, 1.00, 3.00 g/kg) groups. C57BL/6J mice with the same genetic background of same month age were used as control group and control administration (Kaixin San 1.00 g/kg) group, with eight mice in each group. After continuous ig administration for two months, the learning and memory ability of mice was evaluated by Morris water maze test; Hematoxylin-eosin (HE) staining method was used to observe the neuron morphology in hippocampus CA1 area; Congo red staining was used to detect amyloid plaques expression in cortex and hippocampus; Immunohistochemical staining was used to detect amyloid β protein 1-40 (Aβ_1-40), glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) expressions in cortex and hippocampus; ELISA was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in serum and acetylcholine (Ach) level in cortex and hippocampus. Results Compared with model group, learning and memory ability of mice in memantine group and Kaixin San group was significantly improved (P < 0.05, 0.01), number of neurons in hippocampal CA1 area was increased (P < 0.01); Expressions of amyloid plaques, Aβ_1-40, GFAP and Iba-1 in cortex and hippocampus were significantly reduced (P < 0.05, 0.01); Levels of TNF-α, IL-1β and IL-6 in serum were significantly reduced (P < 0.05, 0.01); Ach level in cortex was increased (P < 0.01). Conclusion Kaixin San may prevent and treat AD by inhibiting the activation of astrocytes and microglia, decreasing the levels of inflammatory factors TNF-α, IL-6 and IL-1β in serum, reducing the production of Aβ and amyloid plaques, and increasing the content of Ach.

R285.5

北京市自然科学基金面上项目（7182019）