人参皂苷Rg1对阿尔茨海默症大鼠BDNFTrkB信号通路的影响  

Effects of Ginsenoside Rg1 on BDNF-TrkB Signaling Pathways in Rats with Alzheimer′s Disease

作　　者：陈晓光[1] 潘晓峰[1] 王帆[2] 潘宋斌[1] CHEN Xiaoguang;PAN Xiaofeng;WANG Fan;PAN Songbin(Department of Neurology,Wuhan No.1 Hospital(Wuhan Hospital of Integrated Traditional Chinese Medicine and Western Medicine),Wuhan 430022,China;Department of Geriatric,Wuhan No.1 Hospital(Wuhan Hospital of Integrated Traditional Chinese Medicine and Western Medicine),Wuhan 430022,China)

机构地区：[1]武汉市第一医院(武汉市中西医结合医院)神经内科,武汉430022 [2]武汉市第一医院(武汉市中西医结合医院)老年病科,武汉430022

出　　处：《生物技术进展》2022年第3期446-451,共6页Current Biotechnology

基　　金：湖北省自然科学基金项目(2011CDB299);湖北省卫生和计划生育委员会项目(201742)。

摘　　要：为了探究人参皂苷Rg1对阿尔茨海默症(Alzheimer's disease,AD)大鼠模型脑源性神经营养因子/酪氨酸激酶受体B(BDNF-TrkB)信号通路的影响,选取75只SD大鼠随机分为空白对照组、模型组、低剂量Rg1组、中剂量Rg1组及高剂量Rg1组,每组15只。取各组大鼠脑组织制备脑片,除空白对照组外,其他组加入Aβ1-42试剂制备AD模型,低剂量Rg1组、中剂量Rg1组和高剂量Rg1组分别使用60、120、240μmol·L^(−1) Rg1处理。采用HE染色观察脑组织病理损伤,TUNEL染色检测脑组织细胞凋亡,比色法测定脑片中乙酰胆碱(acetylcholine,Ach)、5-羟色胺(5-hydroxytryptamine,5-HT)水平和乙酰胆碱酯酶(acetylcholinesterase,TChE)活力,蛋白质印迹法检测各组脑片中切割后半胱氨酸蛋白酶-3(Cleaved Caspase-3)、B淋巴细胞瘤-2(B cell lymphoma-2,Bcl-2)、Bcl-2相关蛋白X(Bcl-2 associated X protein,Bax)及BDNF-TrkB信号通路相关蛋白表达情况。与空白对照组相比,模型组脑组织细胞凋亡数、Cleaved Caspase-3、Bax/Bcl-2及TChE水平显著增加,5-HT、Ach、BDNF及TrkB蛋白表达量显著降低(P<0.05);与模型组相比,低剂量Rg1组、中剂量Rg1组和高剂量Rg1组脑组织细胞凋亡数、Cleaved Caspase-3、Bax/Bcl-2及TChE水平显著降低,5-HT、Ach、BDNF及TrkB蛋白表达量显著增加(P<0.05),且具有剂量依赖性。人参皂苷Rg1可有效保护阿尔茨海默症模型大鼠脑组织,抑制神经细胞凋亡,其作用机制可能与激活BDNF-TrkB信号通路相关。通过分析人参皂苷Rg1对AD大鼠模型的保护机制,以期为人参皂苷Rg1用于治疗AD奠定理论基础。The aim of the study is to explore the effects of ginsenoside Rg1 on brain-derived neurotrophic factor/tyrosine kinase re⁃ceptor B(BDNF-TrkB)signaling pathways in rats with Alzheimer's disease(AD).A total of 75 SD rats were enrolled and ran⁃domly divided into blank control group,model group,low-dose Rg1 group,medium-dose Rg1 group and high-dose Rg1 group,with 15 rats in each group.The brain tissues in each group were collected to prepare brain slices.Except blank control group,Aβ1-42 reagent was added into each group to prepare AD models.The low-dose Rg1 group,medium-dose Rg1 group and high-dose Rg group were treated with 60,120 and 240μmol·L^(−1) Rg1,respectively.The pathological damage of brain tissues was observed by HE staining.The apoptosis of brain tissues was detected by TUNEL staining.The levels of acetylcholine(Ach)and 5-hydroxy⁃tryptamine(5-HT),and activity of acetylcholinesterase(TChE)in brain slices were detected by colorimetry.The expressions of cleaved cysteine proteinase-3(Cleaved Caspase-3),B cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax)and BDNF-TrkB signaling pathway related proteins in brain slices were detected by Western blot.Compared with blank control group,the number of brain tissues apoptosis,levels of Cleaved Caspase-3,Bax/Bcl-2 and TChE were significantly increased in model group,and 5-HT,Ach,BDNF and TrkB were significantly decreased in model group(P<0.05).Compared with model group,the number of brain tissues apoptosis,levels of Cleaved Caspase-3,Bax/Bcl-2 and TChE were significantly decreased in low-dose group,medium-dose group and high-dose Rg1 group,and 5-HT,Ach,BDNF and TrkB were significantly increased in low-dose group,medium-dose group and high-dose Rg1 group(P<0.05),which showing concentration-dependence.Ginsenoside Rg1 can effectively protect the brain tissue of AD rats and inhibit neuron apoptosis,which the mechanism of action may be relat⁃ed to activating BDNF-TrkB signaling pathways.By analyzing the protective mechanism of ginsenoside Rg1 on AD rat mode

关 键 词：阿尔茨海默症 人参皂苷RG1 细胞凋亡 BDNF-TrkB信号通路 

分 类 号：R285.5[医药卫生—中药学]