基于BDNF/TrkB/CREB途径探讨固本健脑液改善AD大鼠海马区神经元损伤的内在机制  

Intrinsic Mechanism of Guben Jiannao Decoction in Improving Hippocampal Neuronal Damage of AD Rats based on the BDNF/TrkB/CREB Pathway

作　　者：张誉丹 袁德培 毛剑琴 ZHANG Yu-dan;YUAN De-pei;MAO Jian-qin(School of Basic Medical Sciences,Hubei University of Chinese Medicine,Wuhan 430065,China;Department of Medicine,Hubei Minzu University,Enshi 445000,China)

机构地区：[1]湖北中医药大学基础医学院,湖北武汉430065 [2]湖北民族大学医学部,湖北恩施445000

出　　处：《中药材》2020年第9期2232-2237,共6页Journal of Chinese Medicinal Materials

基　　金：国家自然科学基金资助项目(81860811)。

摘　　要：目的:基于BDNF/TrkB/CREB途径探讨固本健脑液改善AD大鼠海马区神经元损伤的内在机制。方法:建立AD模型,造模成功后随机分为6组,给药组分别灌胃固本健脑方水煎液(2.5、1.25、0.625 g/mL)、盐酸多奈哌齐片(0.045 mg/mL),模型组与正常对照组均灌胃等体积生理盐水。给药结束后,水迷宫检测其学习记忆能力,ELISA检测大鼠海马组织中Aβ_(1-40)、Aβ_(1-42)含量,HE染色观察脑组织海马区病理学变化,流式细胞术检测海马神经元凋亡,RT-PCB和Western blot检测大鼠海马组织中BDNF、TrkB、CREB、p-CREB表达。结果:与正常对照组比较,模型组大鼠逃避潜伏期显著延长,目标象限游泳时间百分比显著降低,海马组织Aβ_(1-40)、Aβ_(1-42)含量及神经元凋亡率显著升高,BDNF、TrkB、CREB、p-CREB mRNA及蛋白表达显著降低(P<0.05或P<0.01);与模型组比较,固本健脑液中、高剂量组及多奈哌齐组逃避潜伏期和目标象限游泳时间均显著改善,海马组织Aβ_(1-40)、Aβ_(1-42)含量及神经元凋亡率显著降低,BDNF、TrkB、CREB、p-CREB mRNA及蛋白表达显著升高(P<0.05或P<0.01)。结论:固本健脑液可通过BDNF/TrkB/CREB信号转导抑制淀粉样蛋白生成途径,从而减轻AD诱导的认知功能障碍。Objective: To explore the intrinsic mechanism of Guben jiannao decoction in improving hippocampal neuronal damage of AD rats based on the BDNF/TrkB/CREB pathway.Methods: AD model was established and the rats were randomly divided into 6 groups after successful modeling.In the administration group, the decoction of Guben jiannao decoction(2.5,1.25,0.625 g/mL)and donepezil hydrochloride tablets(0.045 mg/mL)were administered, respectively.The model group and normal control group were given the same volume of normal saline.After the drug was administered, the water maze tested the ability to learn and remember.The contents of Aβ_(1-40) and Aβ_(1-42) in the hippocampus of rats were measured by ELISA.The pathological changes of hippocampus in brain tissue were observed by HE staining, the apoptosis of hippocampal neurons was detected by flow cytometry, RT-PCB and Western blot were used to detect BDNF,TrkB,CREB,p-CREB expressions in rat hippocampus.Results: Compared with the normal control group, the escape latency of the rats in model group was significantly prolonged, the percentage of swimming time in the target quadrant was significantly reduced, the contents of Aβ_(1-40) and Aβ_(1-42) in the hippocampus and neuronal apoptosis rate were significantly increased, BDNF,TrkB,CREB,p-CREB mRNA and protein expressions were significantly decreased(P<0.05 or P<0.01);Compared with the model group, the escape latency and target quadrant swimming time in the mid-,high-dose of Guben jiannao decoction groups and donepezil group were significantly improved, Aβ_(1-40) and Aβ_(1-42) contents and neuron apoptosis rate were significantly decreased, BDNF,TrkB,CREB,p-CREB mRNA and protein expressions were significantly increased(P<0.05 or P<0.01).Conclusion: Guben jiannao decoction can reduce AD-induced cognitive dysfunction by participating in BDNF/TrkB/CREB signal transduction and inhibiting amyloid production pathway.

关 键 词：固本健脑液 阿尔茨海默病 海马区神经元损伤 BDNF/TrkB/CREB 机制研究 

分 类 号：R285.5[医药卫生—中药学]