基于BDNF/TrkB信号通路的锁阳黄酮对阿尔茨海默病大鼠学习记忆能力的影响  

Effects of Cynomorium songaricum Flavonoids on Learning and Memory Ability of Alzheimer Disease Model Rats Based on BDNF/TrkB Signaling Pathway

作　　者：吕鑫 顾志荣[2] 祁梅[2] 郭燕 毛小文 葛斌[2] LYU Xin;GU Zhirong;QI Mei;GUO Yan;MAO Xiaowen;GE Bin(College of Pharmacy,Gansu University of Chinese Medicine,Lanzhou 730000,China;Gansu Provincial Hospital,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学药学院,甘肃兰州730000 [2]甘肃省人民医院,甘肃兰州730000

出　　处：《中国中医药信息杂志》2023年第7期94-100,共7页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：甘肃省自然科学基金(20JR5RA154);甘肃省青年科技基金(21JR7RA634);甘肃省人民医院青年项目(20GSSY4-29);“白求恩·求索-药学科研能力建设”项目(B-19-H-20200622);甘肃省中药质量与标准研究重点实验室开放基金(ZYZL18-004);甘肃省中药药理与毒理学重点实验室开放基金(ZDSYS-KJ-2018-010)。

摘　　要：目的基于BDNF/TrkB信号通路探讨锁阳黄酮对β淀粉样蛋白(Aβ)1-42诱导的阿尔茨海默病(AD)大鼠学习记忆能力的影响及潜在机制。方法70只SPF级Wistar雄性大鼠随机选取10只作为空白组、10只作为假手术组,余50只采用双侧海马注射Aβ_(1-42)建立AD大鼠模型,将造模大鼠再随机分为模型组、多奈哌齐组(0.5 mg/kg)和锁阳黄酮低、中、高剂量组(25、50、100 mg/kg),连续灌胃相应药液28 d。跳台实验评价大鼠认知功能损伤程度,TUNEL染色观察海马组织细胞凋亡情况,透射电镜观察海马组织神经细胞和突触超微结构变化,ELISA测定海马及血清胆碱乙酰转移酶(ChAT)、乙酰胆碱(ACh)、乙酰胆碱酯酶(AChE)含量,Western blot检测海马组织Bcl-2、Bax、半胱氨酸蛋白酶(Caspase)-3、Caspase-9、脑源性神经营养因子(BDNF)及酪氨酸激酶受体B(TrkB)蛋白表达。结果与假手术组比较,模型组大鼠跳台实验学习和记忆阶段错误次数明显增加,潜伏期明显缩短(P<0.01);海马组织细胞凋亡率明显升高(P<0.01),神经细胞和突触结构严重损伤;海马组织及血清ChAT、ACh含量明显减少(P<0.01),AChE含量明显增加(P<0.01);海马组织Bcl-2、BDNF和TrkB蛋白表达明显降低(P<0.01),Bax、Caspase-3和Caspase-9蛋白表达明显升高(P<0.01)。与模型组比较,锁阳黄酮高剂量组大鼠认知功能损伤程度减轻,海马组织细胞凋亡率降低,神经细胞和突触结构有所改善,海马组织及血清ChAT、ACh含量增加,AChE含量减少,海马组织Bcl-2、BDNF和TrkB蛋白表达升高,Bax、Caspase-3和Caspase-9蛋白表达降低,差异均有统计学意义(P<0.05,P<0.01)。结论锁阳黄酮能明显改善Aβ_(1-42)诱导的AD大鼠认知功能损伤,增加中枢胆碱能系统ACh含量,抑制细胞凋亡及增加突触可塑性,其机制可能与上调海马组织BDNF/TrkB信号通路有关。Objective To investigate the effects and mechanism of Cynomorium songaricum flavonoid(CSF)on Aβ_(1-42)-induced learning and memory ability in rats with Alzheimer disease(AD)based on BDNF/TrkB signaling pathway.Methods A total of 70 SPF Wistar male rats were divided into blank group(10 rats),sham-operation group(10 rats),the remaining 50 AD rat models were established by bilateral hippocampal injection of Aβ_(1-42),and the model rats were randomly divided into model group,donepezil group(0.5 mg/kg)and CSF low-,medium-and high-dosage groups(25,50,100 mg/kg),receiving corresponding drugs by gavage for 28 days.The degree of cognitive impairment was evaluated by platform jumping experiment,TUNEL staining was used to observe the apoptosis of hippocampal cells,ultrastructural changes of neurons and synapses in hippocampal tissue were observed by transmission electron microscopy,the contents of ChAT,ACh and AChE in hippocampal tissue and serum were determined by ELISA,Western blot was used to detect the protein expressions of Bcl-2,Bax,Caspase-3,Caspase-9,BDNF and TrkB in hippocampal tissue.Results Compared with the sham-operation group,the number of errors in learning and memory stages of the platform jumping experiment in the model group significantly increased,and the latency was significantly shortened(P<0.01);the apoptosis rate of hippocampal tissue significantly increased(P<0.01),and nerve cells and synaptic structures were severely damaged;the contents of ChAT and ACh in hippocampal tissue and serum significantly decreased(P<0.01),and the content of AChE significantly increased(P<0.01);the protein expressions of Bcl-2,BDNF and TrkB in hippocampal tissue significantly decreased(P<0.01),while the protein expressions of Bax,Caspase-3 and Caspase-9 significantly increased(P<0.01).Compared with the model group,the degree of cognitive impairment was reduced in the CSF high-dosage group,the apoptosis rate of hippocampal tissue decreased,the ultrastructure of nerve cells and synapses were improved,the contents of ChAT a

关 键 词：锁阳黄酮 阿尔茨海默病 Β淀粉样蛋白 BDNF/TrkB信号通路 海马 大鼠 

分 类 号：R285.5[医药卫生—中药学]