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目的 观察中药益智温胆颗粒对APP/PS1(B6)双转基因小鼠行为学、脑组织病理形态及Aβ的影响.方法 选用APP/PS1(B6)双转基因小鼠随机分为模型组、益智温胆组和多奈哌齐组,将同系背景小鼠作为空白组.益智温胆组、多奈哌齐组以相应药物灌胃,模型组和空白组给予等体积的生理盐水,连续灌胃90天.采用Moms水迷宫测试、跳台测试评估APP/PS1(B6)小鼠行为学;HE染色观察APP/PS1(B6)小鼠海马组织病理变化;ELISA法检测APP/PS1(B6)小鼠海马Aβ含量.结果 Morris水迷宫测试:与空白组比较,模型组小鼠发现平台时间显著延长(P＜0.01),且游泳总路程明显增加(P＜0.01);与模型组比较,给药组小鼠发现平台时间均缩短(P＜0.01),且游泳总路程均减少(P＜0.01).跳台测试:与空白组比较,模型组小鼠出错次数明显增加(P＜0.01),且潜伏期明显缩短(P＜0.01);与模型组比较,给药组小鼠出错次数明显减少(P＜0.01),潜伏期明显延长(P＜0.01).海马组织形态:模型组有明显的脑神经元变性,可见到淀粉样蛋白斑块沉积;多奈哌齐组可看到神经元数量增多且细胞结构排列较整齐;益智温胆组空泡变性和细胞核增大有所改善,神经细胞排列和细胞形态较好.海马Aβ含量:与空白组比较,模型组小鼠海马Aβ1-42和Aβ1-40明显增加(P＜0.01);与模型组比较,益智温胆组和多奈哌齐组小鼠海马组织中的Aβ1-42和Aβ1-40含量明显下降(P＜0.01);与多奈哌齐组比较,益智温胆组小鼠海马组织中Aβ1-42和Aβ1-40含量无明显差异(P＞0.05).结论 益智温胆颗粒有助于提高痴呆小鼠学习记忆能力,可能是通过保护海马神经细胞,降低β样淀粉蛋白沉积实现.“,”Objective To observe the effects ofYizhi Wendan granule on behavior,brain pathological morphology and the content of Aβ in APP/PS 1 (B6) double transgenic mice.Methods 80 APP/PS 1 (B6) double transgenic mice were randomly divided into model group,Yizhi decoction group and donepezil group,with 20 in each group.Mice with syngeneic background were used as blank group.Model group and blank group were given the same volume of physiological saline.The mice in each group were given intragastric administration of 0.2mL/10g for 90d.Morris water maze test and platform test were used to evaluate the behavior of APP/PS1 (B6) mice;the pathological changes of hippocampus in APP/PS1 (B6) mice were observed by HE staining;the content of Aβ in hippocampus ofAPP/PS1 (B6) mice was detected by ELISA method.Results The Morris water maze test results:compared with control group,the time of model group to find the platform significantly was prolonged (P＜0.01),and the total swimming distance was significantly increased (P＜0.01);compared with model group,the time of treatment group to find the platform time was shortened (P＜0.01),and the total swimming distance was reduced (P＜0.05);compared with donepezil group,the time of TCM group to find the platform and swimming distance had no significant difference (P＞0.05).Platform test results:compared with blank group,the number of errors in the platform of model group mice increased significantly (P＜0.01),and the latency was significantly shortened (P＜0.01).Compared with model group,the number of errors in each group was significantly decreased (P＜0.01),and the latency of the mice in donepezil group and Yizhi decoction group was significantly prolonged (P＜0.01).Hippocampal morphology:there was obvious degeneration of brain neuron in model group,and the deposition of amyloid plaques could be seen.In donepezil group,the number of neurons increased and the structure of cells was arranged neatly.The vacuolar degeneration of Yizhi decoction group was improved with the enlargement of nucleus,and the arrangement of nerve cells and the shape of cells was better.Hippocampal Aβ content:compared with control group,hippocampus Aβ1-42 and Aβ1-40 of model group increased significantly (P＜0.01);compared with model group,hippocampus Aβ1-42 and Aβ1-40 of Yizhi group and donepezil group significantly decreased (P＜0.01);compared with donepezil group,there was no significant difference ofhippocampus Aβ1-42 and Aβ1-40 content in Yizhi Wendan group(P＞0.05).Conclusion Yizhi Wendan granule can improve the learning and memory ability of the mice with dementia,which may be achieved by protecting hippocampal neurons and reducing the amyloid beta protein deposition.