| 李 华,赵颖倩,郭 婕,卢苑蓉,张改月,王 强.电针调控Wnt信号改善帕金森病模型小鼠纹状体抑制性突触变性的研究[J].中国康复医学杂志,2023,(10):1336~1343 |
| 电针调控Wnt信号改善帕金森病模型小鼠纹状体抑制性突触变性的研究 点此下载全文 |
| 李 华 赵颖倩 郭 婕 卢苑蓉 张改月 王 强 |
| 陕西中医药大学针灸推拿学院，陕西省咸阳市，712046 |
| 基金项目：国家自然科学基金项目（81674086）；陕西省自然科学基础研究计划（2020JM-594）；陕西中医药大学经脉-脏腑相关研究创新团队（YL-09） |
| DOI：10.3969/j.issn.1001-1242.2023.10.002 |
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| 摘要： |
| 摘要
目的：观察电针对1-甲基-4-苯基-1，2，3，6-四氢吡啶（1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine，MPTP）诱导的帕金森病（Parkinson's disease，PD）模型小鼠纹状体抑制性突触前标志物囊泡γ-氨基丁酸转运蛋白（vesicular GABA transporter，vGAT）、突触后标志物桥尾蛋白（Gephyrin）以及树突棘密度和无翅型MMTV整合位点家族成员5a（wingless-type MMTV integration site family member 5a，Wnt5a）表达的影响，探讨电针改善PD运动功能的部分作用机制。
方法：将雄性C57BL/6小鼠随机分为空白组、模型组、电针组、左旋多巴组，每组10只；除空白组外，MPTP腹腔注射复刻PD小鼠模型。造模成功后第一天对电针组小鼠开始针刺“合谷”“太冲”穴，同日左旋多巴组小鼠腹腔注射左旋多巴注射液，各组小鼠干预2个疗程后采用爬杆及悬挂实验评估各组小鼠运动功能；苏木素伊红染色观察纹状体神经元细胞形态；免疫荧光标记纹状体抑制性突触前标志物vGAT和突触后标志物Gephyrin表达；Western Blot检测纹状体Wnt5a蛋白的表达。
结果：与模型组相比，电针组及左旋多巴组小鼠爬杆耗时缩短（P<0.05），悬挂评分升高（P<0.05）。模型组小鼠神经元细胞稀疏，残留的多巴胺神经元萎缩，胞核皱缩偏移，水肿空泡变性增多；而电针组及左旋多巴组小鼠神经元细胞形态圆润，水肿变性细胞减少，形态清晰。各组小鼠纹状体抑制性突触前标志物vGAT表达无明显差异（P>0.05）。与模型组相比，纹状体神经元树突棘密度增加（P<0.05），电针组及左旋多巴组小鼠纹状体突触后标志物Gephyrin的阳性表达升高（P<0.05），Wnt5a蛋白表达水平升高（P<0.05）。
结论：早期对帕金森病模型小鼠进行电针干预可改善其运动功能障碍，其治疗机制可能是电针激活Wnt5a信号进而调控抑制性突触，改善纹状体GABA能神经元功能。 |
| 关键词：帕金森病 电针 抑制性突触 囊泡γ-氨基丁酸转运蛋白 桥尾蛋白 |
| Regulation of Wnt signal by electroacupuncture improves inhibitory synaptic degeneration of striatum in a mouse model of Parkinson's disease Download Fulltext |
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| College of Acupuncture and Massage， Shanxi University of Traditional Chinese Medicine， Xianyang， Shanxi， 712046 |
| Fund Project: |
| Abstract: |
| Abstract
Objective：To observe the effect of electroacupuncture on the inhibitory presynaptic marker vesicular GABA transporter （vesicular GABA transporter），the postsynaptic marker Gephyrin， and the wingless type MMTV integration site family 5A（wingless type MMTV integration site family） in the striatum of Parkinson's disease （PD） mice induced by 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine（MPTP） and to explore the underlying mechanism of electroacupuncture-induced motor improvement of PD.
Method：Male C57 Black 6 （C57BL/6） mice were randomly divided into blank group， model group， electroacupuncture group and levodopa group， with 10 mice in each group. PD mouse model was duplicated by intraperitoneal injection of MPTP except the blank group. On the first day after successful modeling，mice in the EA group were treated with acupuncture at "Hegu" and "Taichong" points. Mice in the levodopa group were intraperitoneally injected with levodopa injection on the same day. The morphology of striatal neurons was observed by hematoxylin eosin staining. The expressions of inhibitory presynaptic marker vGAT and postsynaptic marker Gephyrin in the striatum were labeled by immunofluorescence. The expression of Wnt5a protein in the striatum was detected by Western Blot.
Result：Compared with the model group， the time of rod climbing was shortened in the EA group or the levodopa group （P<0.05）， and the hanging score was increased （P<0.05）. In the model group， the neuron cells were sparse and the residual dopamine neurons were atrophic with shrunken and shifted nuclei， and the increased edema and vacuolar degeneration. In the EA group and levodopa group， the morphology of neurons was round， edema and degeneration cells were reduced with clear morphology. There was no significant difference in the expression of inhibitory presynaptic marker vGAT in the striatum among all groups （P>0.05）. Compared with the model group， the density of dendritic spines in the striatum neurons was significantly increased （P<0.05）， the positive expression of postsynaptic marker Gephyrin in the striatum was significantly increased （P<0.05）， and the expression level of Wnt5a protein was significantly increased （P<0.05） in the EA or levodopa group
Conclusion：Early electroacupuncture intervention can improve the motor capacity and improve the neuronal morphological structure and function in PD model mice， and the mechanism may include the activation of Wnt5a signaling and the re-promotion of reorganization of functional neuronal circuits in this brain region. |
| Keywords:Parkinson's disease electric acupuncture inhibitory synapse Vesicle-GABA transporter protein Gephyrin |
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