基于CREB/BDNF/TrkB信号通路研究玛咖醇提物改善肾虚衰老记忆减退作用机制  

Exploring the mechanism of Maca ethanol extract improving kidney deficiency aging memory impairment based on CREB/BDNF/TrkB pathway

作　　者：余淑惠 吴晓磊 姜砚馨 张惠 李爱民 邸松蕊 王林元[4] 张建军 费文婷 YU Shuhui;WU Xiaolei;JIANG Yanxin;ZHANG Hui;LI Aimin;DI Songrui;WANG Linyuan;ZHANG Jianjun;FEI Wenting(School of Chinese Medicine,Bejing University of Chinese Medicine,Beijing 102401,China;Guozhen Health Technology(Beijing)Co.,Ltd.Bejing 102206,China;Yantai New Era Health Industry Co.,Ltd.,Yantai 264006,China;School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102401,China)

机构地区：[1]北京中医药大学中医学院,北京102401 [2]国珍健康科技(北京)有限公司,北京102206 [3]烟台新时代健康产业有限公司,烟台264006 [4]北京中医药大学中药学院,北京102401

出　　处：《中华中医药杂志》2023年第12期5742-5747,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81874350);烟台开发区创新创业领军项目(No.2021RC012)。

摘　　要：目的:基于CREB/BDNF/TrkB信号通路研究玛咖醇提物(MEE)改善肾虚衰老记忆减退的作用机制,阐释玛咖补肾益精中医功效内涵。方法:将60只雄性昆明种小鼠随机分为空白组,模型组(氢化可的松琥珀酸钠,25mg/kg),人参组(0.5g/kg),MEE低、高剂量组(0.3、0.6g/kg),造模与给药同时进行,共计14d。采用Morris水迷宫行为学方法观察小鼠记忆能力,ELISA法检测小鼠促肾上腺皮质激素(ACTH)、皮质醇(CORT)、促肾上腺皮质激素释放激素(CRH)水平以及神经递质5-羟色胺(5-HT)、去甲肾上腺素(NE)、多巴胺(DA)的含量,比色法检测氧化应激指标超氧化物歧化酶(SOD)、丙二醛(MDA)的含量,免疫印迹法检测脑组织中脑源性神经营养因子(BDNF)、环磷腺苷效应元件结合蛋白(CREB)、酪氨酸激酶B受体(TrkB)的表达水平。结果:与空白组比较,模型组小鼠到达平台所在象限潜伏期显著升高,且在测试时间内未到达平台所在象限,CRH、ACTH、CORT的含量显著降低,DA及SOD含量显著下降,MDA含量显著升高,CREB、BDNF蛋白表达显著减少(P<0.05,P<0.01)。与模型组比较,各给药组到达平台所在象限潜伏期显著降低(P<0.01),ACTH、CORT含量显著升高,CREB、BDNF蛋白表达升高,MEE高剂量组5-HT、NE、DA及SOD含量显著升高,MEE低剂量组SOD含量显著升高,MDA含量降低(P<0.01,P<0.05)。结论:MEE具有“补肾益精”改善肾虚衰老记忆减退的作用,能够调节HPA轴激素紊乱,其改善记忆的作用机制与抗氧化应激、升高衰老脑内神经递质含量、调控CREB/BDNF/TrkB信号通路,进而提高神经元突触可塑性密切相关。Objective:To explore the mechanism of ethanol extract of Maca(MEE)in improving kidney deficiency and aging memory decline and explain the connotation of kidney-tonifying and essence-enhancing TCM efficacy by the CREB/BDNF/TrkB signaling pathway.Methods:Sixty male Kunming mice were randomly divided into blank group,model group(hydrocortisone sodium succinate,25 mg/kg),ginseng group(0.5 g/kg),MEE low-dose group,MEE high-dose group(0.3,0.6 g/kg).The modeling and drug administration were carried out simultaneously for a total of 14 days.Morris water maze was used to observe the memory ability of mice.The hormone levels of HPA axis(CRH,ACTH,CORT)and the content of neurotransmitters(5-HT,DA,NE)were detected by ELISA.The contents of oxidative stress index(SOD,MDA)were detected by colorimetry,and the expression of CREB/BDNF/TrkB signaling pathway was detected by Western Blot.Results:Compared with the blank group,the latency time of the mice in the model group reached the quadrant where the plaform was located was increased,and did not reach the quadrant during the test time.The contents of CRH,ACTH and CORT were decreased,the contents of DA and SOD were decreased,the content of MDA was increased,and the expression of CREB,BDNF protein were decreased(P<0.05,P<0.01).Compared with the model group,the latency time to reach the target quadrant was shortened in each administration group(P<0.01),the contents of ACTH and CORT were increased,and the expression of CREB,BDNF protein was increased,the contents of 5-HT,NE,DA and SOD in MEE high-dose group were increased,the contents of SOD in MEE low-dose group were increased,the content of MDA in MEE low-dose group was decreased(P<0.01,P<0.05).Conclusion:The MEE can improve the memory decline of kidney deficiency aging by the efficacy of tonifying kidney and strengthening essence,and is able to regulate HPA axis hormone disturbance.The mechanism of improving memory is closely related to anti-oxidative stress,increasing neurotransmitter content in aging brain,regulating CREB/BDNF/Trk

关 键 词：玛咖醇提物 肾虚 衰老 记忆减退 CREB/BDNF/TrkB信号通路 

分 类 号：R285.5[医药卫生—中药学]