开心散对APP/PS1小鼠神经炎症和Aβ沉积的作用研究  

Pharmacological effects of Kaixin San on neuroinflammation and Aβdeposition in APP/PS1 mice

作　　者：王彬斌 冯晓晓 恩特扎尔·别尔克 赵晖[1] 李朝霞[1] WANG Bin-bin;FENG Xiao-xiao;Entzal Berk;ZHAO Hui;LI Zhao-xia(Beijing Key Laboratory of TCM Collateral Disease Theory Research,School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学中医药学院,中医络病研究北京市重点实验室,北京100069

出　　处：《中草药》2021年第24期7511-7519,共9页Chinese Traditional and Herbal Drugs

基　　金：北京市自然科学基金面上项目(7182019)。

摘　　要：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(amyloidβprotein 1-40,Aβ1-40)、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、Aβ1-40、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 amyloidβprotein 1-40(Aβ1-40),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,Aβ1-40,GFAP and Iba-1 in cortex and hippocampus were significantly reduced(P<0.05,0.01);Levels of TNF-α,IL-1βand 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-1βin serum,reducing the production of Aβand amyloid plaques,and increasing the content of Ach.

关 键 词：开心散 阿尔茨海默症 淀粉样前体蛋白/早老素基因1双转基因小鼠 Β淀粉样蛋白 胶质纤维酸性蛋白 离子钙接头结合调节分子-1 

分 类 号：R285.5[医药卫生—中药学]