目的:研究中药复方-还脑益聪方(HNYCF)组分对阿尔茨海默病(AD)动物模型脑组织炎症因子和氧化应激相关指标的影响,探讨其治疗AD的作用机制.方法:选用3月龄APP695V717I转基因小鼠AD模型,随机分成4组:模型组、盐酸多奈哌齐组、HNYCE组分大剂量组和HNYCF组分小剂量组.另设立正常对照组(相同遗传背景的C57BL/6J小鼠).各组小鼠按相应处理连续灌胃6个月后进行相关指标检测.采用Morris水迷宫和跳台实验观测小鼠学习记忆能力,采用免疫组织化学法检测脑组织核因子κB(NF-κB)和过氧化物酶体增殖物激活受体γ(PPARγ)的表达水平,放射免疫法测定脑组织皮层和海马白细胞介素-6(IL-6)和高敏C-反应蛋白(hs-CRP)的含量,比色法检测血清超氧化物歧化酶(SOD)活性,硫代巴比妥酸法测定血清丙二醛(MDA)含量.结果:HNYCF小鼠在Morris水迷宫中穿越平台次数、第4象限游泳时间和路程均较模型组显著增多(P<0.05或P<0.01);HNYCF大剂量组小鼠在跳台实验中潜伏期较模型组显著延长(P<0.01);HNYCF小鼠脑组织NF-κB表达下调,PPARγ表达上调,IL-6含量减少,与模型组比较有显著差异(P<0.05或P<0.01);HNYCF小鼠血清SOD活性较模型组显著升高(P<0.05或P<0.01).结论:HNYCF可以改善APP转基因小鼠的学习记忆能力,其作用机制可能与抗炎、抗氧化作用有关.%AIM: To study the effects of Chinese herbal compound Huannaoyicongfang ( HNYCF ) on inflammatory reaction and oxidative stress in the brain of Alzheimer's disease ( AD ) animal model, and to explore its role in treating AD.METHODS: APP695V717I transgenic mice ( 3 months old ),as an AD model in this study, were randomly divided into model group, donepezil group, HNYCF high - dose group and HNYCF low - dose group.C57BL/6J mice, which were of the same age and genetic background as the transgenic mice, were used as controls.The animals were administered intragastrically with the drug or water from 3 months old to 9 months old.Morris water maze test was performed to measure the spatial learning and memory ability.Step - down test was performed to observe the learning and memory ability of single passive avoidance response.The expression of nuclear factor kappa B ( NF - κB ) and peroxisome proliferator - activated receptor γ ( PPARγ ) in hippocampus CA1 region was detected by immunohistochemistry with image analysis.The levels of interleukin - 6 ( IL - 6 ) and high sensitivity C - reactive protein ( hs - CRP ) in the brain cortex and hippocampus homogenate were measured by radioimmunoassay.The activity of superoxide dismutase ( SOD ) in serum was detected by colorimetry.The content of malondialdehyde ( MDA ) in serum was detected by thibabituric acid method.RESULTS: Morris water maze test showed that the times of crossing platform, and the swimming time and distance in the fourth quadrant in HNYCF groups were much more than those in model group.The step - down test manifested that the escape latency in HNYCF high - dose group was significantly longer than that in model group.Compared with model group, the expression of NF - κB obviously decreased, the expression of PPARγ significantly increased and the content of IL - 6 was lower in HNYCF groups.The activity of serum SOD in HNYCF groups was significantly higher than that in model group.CONCLUSION: HNYCF evidently ameliorates the learning and memory ability in APP transgenic mice, which may be related to the anti - inflammatory and anti - oxidation effects of HNYCF.
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