姜黄素对阿尔茨海默病模型小鼠病情效果的改善作用及相关机制研究

Treatment effect of curcumin on Alzheimer＇s disease in mice and its related mechanism

目的探讨姜黄素改善阿尔茨海默病（AD）模型小鼠病情的效果以及相关机制，为AD的治疗提供实验依据。方法将48只昆明种APP／PSI双转基因小鼠按随机数字表法分成4组，即AD模型组、AD模型＋低剂量姜黄素组、AD模型＋中剂量姜黄素组、AD模型＋高剂量姜黄素组，每组各12只，后3组同时腹腔注射剂量分别为100mg／（b·d）、200mg／（kg·d）、400mg／（kg·d）姜黄素（1次／d，连续14d1。另取正常小鼠12只做为正常对照组，不做任何处理。应用牵引实验、Morris水迷宫实验检测各组小鼠行为学改变，免疫组化染色检测各组小鼠脑组织Shankl、PSD95阳性表达．Western blotting法检测各组小鼠脑组织Shankl、PSD95蛋白表达。结果AD模型组和AD模型＋低剂量姜黄素组的牵引实验平均得分、逃避潜伏期、通过原平台次数、原平台所在象限停留时间百分比以及Shankl、PSD95免疫组化染色阳性率与正常对照组比较差异均具有统计学意义（P〈0．05）；AD模型＋中剂量姜黄素组的牵引实验平均得分、逃避潜伏期、通过原平台次数、原平台所在象限停留时间百分比以及Shankl、PSD95免疫组化染色阳性率与AD模型组比较差异具有统计学意SL（P〈0．05）；AD模型＋低剂量姜黄素组、AD模型＋中剂量姜黄素组和AD模型＋高剂量姜黄素组Shankl、PSD．95蛋白表达与AD模型组比较差异具有统计学意义（P〈0．05）。结论应用中剂量姜黄素可更好地改善AD模型小鼠的运动能力、学习能力及记忆能力，其机制可能是通过改善突触相关蛋白Shankl、PSD95表达及突触结构，提高AD模型小鼠海马突触数量，进而改善突触的可塑性。

Objective To investigate the treatment effect ofcurcumin on Alzheimer＇s disease in mice and its related mechanism to provide a theoretical reference for the treatment of AD. Methods Forty-eight Kunming mice with APP/PSI transgenosis were randomly divided into four groups： AD model group, AD model＋low-dose curcumin group, AD model＋middle-dose curcumin group, AD model＋high-dose curcumin group （n=12）; mice in these later three groups were intraperitoneally injected curcumin at the dosages of 100 mg/（kg, d）, 200 mg/（kg·d） and 400 mg/（kg, d）, respectively （once diary for a consecutive 14 d）.Another 12 healthy mice were selected as normal control group.Traction test and Morris water maze test were used to observe the behavioral changes of mice in each group; immunohistochemical staining was used to detect the Shankl and PSD95 expressions in brain tissues of mice in each group; and Western blotting was used to detect the Shankl and PSD95 protein expression. Results There were significant differences between normal control group and both AD model group and AD model＋low-dose curcumin group in average scores, escape latency and frequency through the original platform and dwell time percentages in the original platform quadrant in the traction experiments, positive cell counts and average gray scale of Shankl and PSD95 （P〈0.05）. Significant differences werenoted between AD model＋middle-dose curcumin group and AD model group in average scores, escape latency and frequency through the original platform, dwell time percentages in the original platform quadrant in traction experiments, positive cell counts and average gray scale of Shankl and PSD95 （P〈0. 05）. As compared with AD model group, the AD model＋low-dose curcumin group, AD model＋middle-dose curcumin group and AD model＋high-dose curcumin group showed significantly different Shankl and PSD95 protein expressions （P〈0.05）. Conclusion The middle-dose curcumin application can better improve athletic ability, learning ability and memory capacity of the AD model mice, whose mechanism may be the improvement of shankl and PSD9 related synaptic and synaptic structure to increase the number of synapses in hippocampus of AD model mice, thereby improving synaptic plasticity.