CRMP2衍生的TAT-CBD3多肽对阿尔茨海默病神经元的保护作用

Protective effect of CRMP2-derived peptides on neurons in Alzheimer’s disease

目的探索CRMP2衍生的TAT-CBD3多肽对AD大鼠神经元的保护作用及其机制。方法雄性Wistar大鼠随机分为假手术组(Sham)、模型组(Model)、TAT-CBD3高剂量组(10mg/kg)以及TAT-CBD3低剂量组(3mg/kg)。制备大鼠阿尔茨海默病模型,模型成功后,尾静脉注射给药,连续给药15天,假手术组及模型组给予相同体积的生理盐水。末次给药后,Morris水迷宫进行大鼠行为学检测,HE染色检测大鼠海马CA1区神经元损伤,Western blot法检测相关蛋白表达,免疫共沉淀法检测蛋白相互作用。结果TAT-CBD3多肽能够明显改善大鼠学习和记忆能力,减轻海马CA1区神经元损伤,降低pCRMP2、NMDAR2B蛋白表达,抑制pCRMP2与NMDAR2B之间相互作用(P<0.01,P<0.05)。结论CRMP2衍生的TAT-CBD3多肽能够改善阿尔茨海默病症状,减轻神经元损伤,其机制可能与抑制pCRMP2、NMDAR2B蛋白表达,干扰两者相互作用有关。

Objective To explore the protective effect of CRMP2-derived peptide TAT-CBD3on AD rat neurons and its mechanism.Methods Male Wistar rats were randomly divided into four groups:sham group,model group,TATCBD3-H group(10mg/kg)and TAT-CBD3-L group(3mg/kg).After the rat model of Alzheimer's disease was established,the rats were given the drugs by tail vein for 15days.The rats in sham group and the model group were given the same volume of saline.After the last administration,Morris water maze was used to detect rat behavior,HE staining was used to detect neuronal damage in hippocampal CA1area,Western blot was used to detect the expression of proteins,and immunoprecipitation was used to detect protein interaction.Results TAT-CBD3peptides could significantly improve the learning and memory ability of rats,alleviate neuronal damage in hippocampal CA1region,reduce the expression of pCRMP2and NMDAR2Bprotein,and inhibit the protein interactions between pCRMP2and NMDAR2B(P<0.01,P<0.05).Conclusion The TAT-CBD3peptides derived from CRMP2can improve the symptoms of Alzheimer's disease and alleviate neuronal damage.Its mechanism may be related to inhibiting the expression of pCRMP2and NMDAR2Bproteins and interfering with their interaction.