电针对帕金森病模型小鼠纹状体BDNF/GSK-3β信号通路影响  

Effect of Electroacupuncture on BDNF/GSK-3βSignaling Pathway in Striatum of Parkinson's Disease Model Mice

作　　者：李媛媛 包小立[2] 汪瑶 王彦春 LI Yuanyuan;BAO Xiaoli;WANG Yao;WANG Yanchun(Yongzhou Hospital of Traditional Chinese Medicine Affiliated to Hunan Medical College,Yongzhou 425799,Hunan,China;Hubei University of Traditional Chinese Medicine,Wuhan 430060,Hubei,China)

机构地区：[1]湖南医药学院附属永州市中医医院,湖南永州425799 [2]湖北中医药大学,湖北武汉430060

出　　处：《辽宁中医药大学学报》2025年第3期33-38,共6页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(30973809);国家自然科学基金青年科学基金项目(30300461)。

摘　　要：目的探讨电针对1-甲基-4-苯基-12,3,6-四氢吡啶(MPTP)诱导的帕金森病(Parkinson's disease,PD)模型小鼠纹状体脑源性神经营养因子(BDNF)及磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)、细胞外调节蛋白激酶(ERK1/2)信号通路蛋白表达的影响。方法将30只SPF级C57/BL6雄性小鼠随机分为对照组(Ctrl组)、模型组(PD组)、电针组(EA组),每组10只。采用MPTP腹腔注射建立PD小鼠模型。电针组每日给予电针“风府”“太冲”“足三里”治疗30 min,持续治疗12 d。采用爬杆、悬挂、旷场实验观察小鼠行为学变化,免疫组化法检测纹状体平均吸光度,实时荧光定量PCR法检测纹状体中酪氨酸羟化酶(TH)、PI3K、AKT和糖原合成酶激酶-3β(GSK-3β)的mRNA表达,蛋白质印迹法检测纹状体TH、p-ERK1/2、BDNF、GSK-3β及凋亡蛋白Bcl-关联X蛋白(Bax)、B淋巴细胞瘤-2基因(Bcl-2)的蛋白表达。结果与Ctrl组相比,PD组爬杆、悬挂实验时间均延长(P<0.01),旷场运动距离明显缩短(P<0.01),存在四肢动作不协调、运动迟缓无力等症状;TH平均吸光度显著降低(P<0.01);TH、PI3K、AKT mRNA表达下降(P<0.01),而GSK-3βmRNA表达升高(P<0.05);TH、p-ERK1/2、BDNF、Bcl-2蛋白水平均降低,而GSK-3β与Bax蛋白水平均提高。与PD组相比,EA组爬杆、悬挂实验时间显著缩短(P<0.01),旷场运动距离有所延长(P<0.05);TH平均吸光度显著提高(P<0.01);TH、PI3K、AKT mRNA表达均升高(P<0.01),而GSK-3βmRNA表达下降(P<0.05);TH、p-ERK1/2、BDNF、Bcl-2蛋白水平均有所提高,而GSK-3β与Bax蛋白水平有所降低。结论电针通过调控BDNF,激活PI3K/AKT与ERK1/2通路,抑制GSK-3β活性以减少细胞凋亡,缓解帕金森病小鼠运动障碍,发挥神经保护作用。Objective To investigate the effect of electroacupuncture on the protein expression of BDNF,PI3K/AKT and ERK1/2 signaling pathways in the striatum of mice with Parkinson's disease(PD)induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Methods A total of 30 SPF C57/BL6 male mice were randomly divided into control group(Ctrl group),model group(PD group)and electroacupuncture group(EA group),with 10 mice in each group.The PD mouse model was established by intraperitoneal injection of MPTP.The EA mouse model was applied to“Fengfu(GV20)”“Taichong(LR3)”and“Zusanli(ST36)”for 30 min daily for 12 days.The behavioral changes of mice were observed by climbing pole test,suspension test and open field test.The mean optical density of striatum was detected by immunohistochemistry.The mRNA expression of TH,PI3K,AKT and GSK-3βin striatum was detected by real-time fluorescence quantitative PCR.The protein expressions of TH,p-ERK1/2,BDNF,GSK-3β,Bax and Bcl-2 in striatum were detected by Western blotting.Results Compared with the Ctrl group,the PD group had longer pole climbing and suspension test time(P<0.01),and the open field movement distance was significantly shortened(P<0.01),with symptoms such as incoordination,bradykinesia and weakness of limbs.The mean optical density of TH decreased significantly(P<0.01);TH,PI3K,AKT mRNA expression decreased(P<0.01),while GSK-3βmRNA expression increased(P<0.05);The protein levels of TH,p-ERK1/2,BDNF and Bcl-2 were decreased,while the protein levels of GSK-3βand Bax were increased.Compared with the PD group,the EA group had significantly shorter climbing pole and hanging test time(P<0.01),and the open field movement distance was prolonged(P<0.05);The mean optical density of TH increased significantly(P<0.01);TH,PI3K,AKT mRNA expression increased(P<0.01),while GSK-3βmRNA expression was decreased(P<0.05);The protein levels of TH,p-ERK1/2,BDNF and Bcl-2 were increased,while the protein levels of GSK-3βand Bax were decreased.Conclusion Electroacupuncture plays a neuroprot

关 键 词：帕金森病 电针 神经营养因子 

分 类 号：R245.97[医药卫生—针灸推拿学]