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目的研究中药复方金思维对APPV717Ⅰ转基因小鼠海马神经损伤的保护作用。方法将3月龄的APPV717Ⅰ转基因小鼠随机分为模型组,多奈哌齐治疗组(0.92 mg/kg),金思维小、中、大剂量(0.075、0.15、0.3g/kg)治疗组,并以同月龄遗传背景相同的C57BL/6J小鼠作为正常对照组,每组6只,每天ig给药1次。给药8个月后(11月龄)用Morris水迷宫进行行为学测试,用电镜观察海马CA1区超微结构变化,同时用免疫组化方法观察海马CA1区Shank1蛋白的表达变化。结果行为学检测显示,金思维治疗组与模型组相比逃避潜伏期显著缩短(P<0.05),目标象限游泳时间明显延长(P<0.05、0.01),并且与对照组比较无显著差异。海马超微结构显示,模型组小鼠海马CA1神经元出现明显变性及坏死,突触结构不完整,数量明显减少。而金思维各剂量组与模型组相比,剂量依赖性的减轻神经元变性、坏死,增加突触的数目。突触相关蛋白Shank1,模型组小鼠海马CA1区Shank1阳性细胞总数、总面积以及阳性细胞积分吸光度与对照组相比明显减少(P<0.05、0.01),而金思维治疗组与模型组相比能显著提高Shank1阳性细胞总数、总面积以及阳性细胞积分吸光度(P<0.05、0.01)。结论金思维能明显改善APPV717Ⅰ转基因小鼠海马神经损伤,增加突触相关蛋白Shank1的表达,进而改善了APPV717Ⅰ转基因小鼠的学习记忆能力。
Objective To study the protective effect of traditional Chinese medicine compound golden thinking on hippocampal neural injury in APPV717I transgenic mice. METHODS: Three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil treatment group (0.92 mg/kg), and small-, medium-, and high-dose (0.075, 0.15, and 0.3 g/kg) treatment groups in the same month. C57BL/6J mice with the same genetic background were used as normal control groups, 6 mice in each group and ig administration once daily. Eight months later (11 months of age), behavioral tests were performed using Morris water maze. The ultrastructure of hippocampal CA1 region was observed by electron microscopy, and the expression of Shank1 protein in hippocampal CA1 region was observed by immunohistochemistry. RESULTS: Behavioral tests showed that the latency to escape was significantly shorter in the Jinzhi treatment group than in the model group (P<0.05), swimming time in the target quadrant was significantly longer (P<0.05, 0.01), and there was no significant difference compared with the control group. The ultrastructure of the hippocampus showed that the CA1 neurons of the mouse hippocampus in the model group showed marked degeneration and necrosis, and the synapse structure was incomplete and the number was significantly reduced. Compared with the model group, the dose-dependent reduction of neuron degeneration and necrosis and the increase in the number of synapses were observed in each dose group of Golden Thinking. The number of Shank1 positive cells in the synapse-associated protein Shank1 and the hippocampal CA1 region in the model group was significantly lower than that in the control group (P<0.05, 0.01), and compared with the model group in the gold thinking treatment group. Can significantly increase the total number of Shank1 positive cells, the total area and positive cells integrated absorbance (P <0.05, 0.01). Conclusions Golden Thinking can significantly improve the hippocampal nerve injury in APPV717I transgenic mice, increase the expression of synapse-associated protein Shank1, and improve the learning and memory ability of APPV717I transgenic mice.