电针对帕金森病小鼠碱性成纤维细胞生长因子/糖原合成酶激酶-3β通路的调控作用OA北大核心
Effect of electroacupuncture on regulation of the basic fibroblast growth factor/glycogen synthase kinase-3β pathway in Parkinson's disease mice
目的:观察电针对帕金森病(PD)小鼠碱性成纤维细胞生长因子(BFGF)/糖原合成酶激酶-3β(GSK-3β)通路的影响,探讨电针治疗PD的相关机制.方法:将C57/BL6雄性小鼠按随机数字表法分为对照组、模型组、电针组、抑制剂组、抑制剂+电针组,每组10只.采用甲基-4-苯基-1,2,3,6-四氢吡啶腹腔注射建立PD小鼠模型.电针组电针"风府""太冲""足三里"干预,每次30 min,每日1次,治疗12 d.抑制剂组予成纤维细胞生长因子受体(FGFR)抑制剂AZD4547(12.5 mg·kg-1·d-1)连续灌胃12 d.抑制剂+电针组在抑制剂组的基础上给予电针治疗.敞箱实验观察小鼠自主运动能力,免疫组织化学法检测小鼠中脑黑质酪氨酸羟化酶(TH)表达量,TUNEL法检测小鼠黑质组织细胞凋亡率,Western blot法检测中脑黑质BFGF、磷酸化磷脂酰肌醇3-激酶(p-PI3K)、磷酸化蛋白激酶B(p-AKT)、p-GSK-3β、B淋巴细胞瘤-2(Bcl-2)、Bcl-相关X蛋白(Bax)蛋白相对表达量.结果:与对照组比较,模型组敞箱实验自主运动总路程明显缩短(P<0.01),静止持续时间明显延长(P<0.01),中脑黑质TH阳性表达降低(P<0.01),中脑黑质细胞凋亡率升高(P<0.01),BFGF、p-PI3K、p-AKT、p-GSK-3β、Bcl-2蛋白相对表达量降低(P<0.01),Bax蛋白相对表达量升高(P<0.01).与模型组和抑制剂+电针组相比,电针组敞箱实验自主运动总路程明显延长(P<0.01),静止持续时间明显缩短(P<0.01),中脑黑质TH阳性表达升高(P<0.05),细胞凋亡率降低(P<0.01,P<0.05),BFGF、p-PI3K、p-AKT、p-GSK-3β、Bcl-2蛋白相对表达量升高(P<0.01,P<0.05),Bax蛋白相对表达量降低(P<0.05).结论:电针"风府""太冲""足三里"可缓解PD小鼠运动障碍,减轻细胞凋亡,其机制可能与调控BFGF/GSK-3β通路有关.
Objective To observe the effect of electroacupuncture(EA)on basic fibroblast growth factor(BFGF)/glycogen synthase kinase-3β(GSK-3β)pathway in Parkinson's disease(PD)mice,so as to explore the potential mechanisms of EA in treating PD.Methods Fifty C57/BL6 male mice were randomly divided into the control,model,EA,inhibitor and EA+inhibitor(combination)groups,with 10 mice in each group.The PD mouse model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.Mice in the EA group received EA stimulation at"Fengfu"(GV16),"Taichong"(LR3)and"Zusanli"(ST36)for 30 min,once daily for 12 days.The inhibitor group received gavage of fibroblast growth factor receptor(FGFR)inhibitor AZD4547(12.5 mg·kg-1·d-1)for 12 consecutive days.The open box experiment was used to observe the autonomous movement ability of mice.The expression level of tyrosine hydroxylase(TH)in substantia nigra was detected by immunohistochemistry.The apoptosis rate of substantia nigra cells was measured by TUNEL method.The relative protein expression levels of BFGF,phosphorylated phosphatidylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-AKT),p-GSK-3β,B-lymphomatoma-2 gene(Bcl-2),and Bcl associated X protein(Bax)in substantia nigra were detected by Western blot.Results After modeling,compared with the control group,the total movement distance was shorten and the duration of rest was prolonged in the open box experiment(P<0.01),the average absorbance of TH in the substantia nigra of the midbrain was decreased(P<0.01),and the apoptosis rate of substantia nigra cells in the midbrain was increased(P<0.01),the protein expression levels of BFGF,p-PI3K,p-AKT,p-GSK-3β and Bcl-2 were decreased(P<0.01),while the expression level of Bax protein was increased(P<0.01)in the model group.Compared with the model and the combination groups,the total movement distance was prolonged and the duration of rest was shorten(P<0.01),the average absorbance of TH was increased(P<0.05),and the apoptosis rate was decreased(P<0.01,P<0.05),the expression levels of BFGF,p-PI3K,p-AKT,p-GSK-3β and Bcl-2 were increased(P<0.01,P<0.05),while the expression level of Bax was decreased(P<0.05)in the EA group.Conclusion EA at GV16,LR3 and ST36 can alleviate motor disorders,reduce cell apoptosis,protect dopaminergic neurons in mice with PD,which may be related to its effect in regulating the BFGF/GSK-3β pathway.
李媛媛;包小立;汪瑶;王彦春
湖北中医药大学针灸骨伤学院,武汉 430060湖北中医药大学针灸骨伤学院,武汉 430060湖北中医药大学针灸骨伤学院,武汉 430060湖北中医药大学中医临床学院,武汉 430060
帕金森病电针碱性成纤维细胞生长因子糖原合成酶激酶-3β
Parkinson's diseaseElectroacupunctureBasic fibroblast growth factorGlycogen synthase kinase-3β
《针刺研究》 2025 (2)
167-173,7
国家自然科学基金项目(No.30973809)国家重点研发计划项目(No.2020YFC0845800)
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