【作者】 伍文彬； 李斌； 王飞； 王永炎；

【Author】 WU Wen-bin;LI Bin;WANG Fei;WANG Yong-yan;Chengdu University of TCM;China Academy of Chinese Medical Sciences;

【机构】 成都中医药大学； 中国中医科学院；

【摘要】 目的:探讨黄连解毒汤（HJD）对Aβ_25-35诱导AD大鼠学习记忆能力和相关蛋白激酶表达的影响。方法:SD雄性大鼠72只,随机分为假手术组、模型组、阳性药多奈哌齐组、黄连解毒汤高、中、低剂量组（6、3、1.5g/kg）,每组12只。除假手术组外,在大鼠双侧海马区立体定向注射Aβ_25-35诱导AD大鼠模型,假手术组定向注射0.9%氯化钠溶液。术后连续灌胃30d,进行Morris水迷宫实验,测试结束后处死动物,摘全脑采用免疫组化和蛋白印迹法检测皮层相关蛋白激酶GSK-3β和CDK-5的表达。结果:黄连解毒汤可缩短AD大鼠平均逃避潜伏期（P<0.05,P<0.01）,增加经过逃逸平台次数（P<0.05）、延长有效区停留时间及有效区游泳路程（P<0.05,P<0.01）,有效抑制大鼠脑内GSK-3β及CDK-5蛋白的表达（P<0.05,P<0.01）。结论:黄连解毒汤能够改善Aβ_25-35诱导AD模型大鼠的学习记忆能力,具有较好的益智作用,其机制可能与抑制脑内tau蛋白磷酸化关键蛋白激酶GSK-3β及CDK-5的活性,进而调控tau蛋白磷酸化水平,从而减少NFT在细胞内聚积有关。更多还原

【Abstract】 Objective:To investigate the effects of Huanglian Jiedu Decoction（HJD） on learning and memorizing ability and expression of the related protein kinase in AD rats induced by Aβ_25-35.Methods:72 male SD rats were randomly divided into six groups:a sham-operation group,a model group,donepezil group,HJD at a high dose group（6g/kg）,HJD at a medium dose group（3g/kg） and HJD at a low dose group（1.5g/kg）,with 12 rats in each group.The rats in sham-operated group were injected with normal saline（NS）,and the rats in other groups were injected with Aβ_25-35 in hippocampus.The rats were given corresponding drug by gavage once a day for 30 days after surgery.The rats’ learning and memorizing ability were evaluated by the Morris water maze.Then they were sacrificed and their brains were taken for determination of the cortical GSK-3P and CDK-5 expression by immunohistochemistry and western blotting.Results:Huanglian Jiedu Decoction decreased the mean escape latency in directional navigation test（P<0.05,P<0.01）,increased the times of traversing platform（P<0.05）,and increased the effective quadrant dwell time and swimming distance in space exploration test（P<0.05,P<0.01）.It also inhibited the protein expression of cortical GSK-3β and CDK-5 in brain tissues（P<0.05,P<0.01）.Conclusion:Huanglian Jiedu Decoction can improve learning and memorizing ability of AD rat models.This effect might be related to inhibiting the activation of cortical GSK-3β and CDK-5 regulating the level of phosphorylation of tau protein and reducing the formation of NFT.更多还原