板桥党参通过PP2A信号通路改善AD模型大鼠认知功能障碍  

Banqiao Codonopisis Pilosula improves cognitive dysfunction in AD model rats by PP2A signaling pathway

作　　者：谌勤 罗洪斌 谢文执 CHEN Qin;LUO Hong-bin;XIE Wen-zhi(Dept of Biochemistry and Molecular Biology, Medical College, Hubei University for Nationalities, Enshi Hubei 445000,China;Dept of Biochemistry and Molecular Biology,Science and Technology College,Hubei University for Nationalities, Enshi Hubei 445000,China;Institute of Neurological and Psychiatric Comorbidity, Hubei University for Nationalities, Enshi Hubei 445000,China)

机构地区：[1]湖北民族大学医学部生物化学与分子生物学教研室,湖北恩施445000 [2]湖北民族大学科技学院生物化学与分子生物学教研室,湖北恩施445000 [3]湖北民族大学神经精神共患病研究所,湖北恩施445000

出　　处：《中国药理学通报》2019年第9期1232-1239,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81260172,81660223);湖北省自然科学基金面上项目(No 2017CFB451);湖北民族大学博士基金启动项目(No MY2012B015)

摘　　要：目的探讨板桥党参(BCP)对冈田酸(OA)诱导的阿尔茨海默病(AD)大鼠认知功能的保护作用及其可能机制。方法将SD大鼠随机分为DMSO组﹑OA组﹑BCP低、中、高治疗组,每组分1周和2周组灌胃。水迷宫训练5 d,训练结束24 h后造模,DMSO组大鼠双侧脑海马各注射10%DMSO 1.5μL,OA组和BCP治疗组同位置注射OA(0.392 mmol·L^-1)1.5μL。造模后,水迷宫测试观察大鼠空间学习能力;Western blot检测各组海马PP2A活性、Tau蛋白磷酸化水平及突触蛋白表达情况;尼氏染色观察大鼠海马CA1﹑CA3区尼氏小体变化情况。结果水迷宫实验发现,BCP能改善AD大鼠空间记忆障碍;Western blot结果显示,BCP能提高PP2A活性,增加突触蛋白表达量,同时减少Tau蛋白磷酸化水平。尼氏染色提示,BCP治疗组尼氏小体数量增加。结论BCP能上调PP2A活性,降低Tau蛋白的磷酸化水平,同时提高突触相关蛋白表达水平,修复受损神经元。Aim To investigate the protective effect of Banqiao Codonopsis pilosula (BCP) on cognitive function in rats with Alzheimer′s disease(AD) induced by Okadaic acid(OA) and its possible mechanism. Methods SD rats were randomly divided into DMSO group, OA group and BCP low, medium, high treatment group. The rats were gavage administered in groups of one week and two weeks. The water maze training was continued for five days before modeling, and modeling was started 24 hours after the training. The bilateral hippocampus of DMSO group was injected with 10% DMSO 1.5 μL. OA group and BCP treatment group were injected with OA(0.392 mmol·L ^-1 ) 1.5 μL. The water maze test was used to observe the spatial learning ability of rats. Western blot was used to observe the activity of PP2A, the phosphorylation of Tau protein and the expression of synaptic protein in hippocampus, and the Nissl′s staining to observe the changes of Nissl bodies in hippocampus CA1 and CA3. Results Water maze experiments showed that BCP could improve spatial memory impairment in AD rats. Western blot results showed that BCP increased PP2A activity, increased synaptic protein expression, and decreased Tau protein phosphorylation. Nissl′s staining suggested an increase in the number of Nissl bodies in BCP treatment group. Conclusions BCP can up-regulate PP2A activity, decrease the phosphorylation level of Tau protein, increase the expression of synaptic proteins, and repair damaged neurons.

关 键 词：阿尔茨海默病 板桥党参 PP2A TAU磷酸化 尼氏染色 认知功能 

分 类 号：R282.71[医药卫生—中药学] R322.81[医药卫生—中医学]