电针对帕金森病小鼠MMP-2/9通路介导的血脑屏障通透性的影响

IF 1.3 4区医学 Q4 INTEGRATIVE & COMPLEMENTARY MEDICINE

World Journal of Acupuncture-Moxibustion Pub Date : 2025-01-01 DOI:10.1016/j.wjam.2025.01.002

Xiao-lei ZHANG (张小蕾), Meng-ni HU (胡梦妮), Ya-nan LI (李亚楠), Yao WANG (汪瑶), Zhen RONG (荣臻), Jun MA (马骏)

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After successfully modeled, in the EA group and EA + SB-3CT group, EA was conducted at “Fengfu (GV16)” and bilateral “Taichong (LR3)” and “Zusanli (ST36)”, at 1 mA and 2 Hz for 30 min each time, once a day, for consecutive 2 wk. The behavioral changes of the mice were observed in each group using the open field test, the level of tyrosine hydroxylase (TH) in the substantia nigra was determined by immunohistochemistry, the permeability of the blood-brain barrier was detected by Evans blue staining, and the protein expression of ZO-1, ocludin, claudin-1, MMP-2 and MMP-9 in the substantia nigra was detected by Western blotting.</div></div><div><h3>Results</h3><div>Compared with the NC group, the behavioral scores increased (<em>P</em> < 0.05), while total time of locomotion, total distance and average speed were reduced (<em>P</em> < 0.05) in the PD group. The expression of TH in the substantia nigra decreased (<em>P</em> < 0.05), Evans blue level in the brain tissue increased (<em>P</em> < 0.05), and the protein expression of ZO-1, occludin and claudin-1 was lower (<em>P</em> < 0.05), whereas MMP-2 and MMP-9 expression was higher (<em>P</em> < 0.05) in the PD group. Compared with the PD group, behavioral scores decreased (<em>P</em> < 0.05), while the total time of locomotion, total distance and average speed increased (<em>P</em> < 0.05) in the EA group. Additionally, TH expression in the substantia nigra was elevated (<em>P</em> < 0.05), Evans blue level in the brain tissue was lower (<em>P</em> < 0.05), the protein expression of ZO-1, occludin and claudin-1 was up-regulated (<em>P</em> < 0.05), and MMP-2 and MMP-9 expression was down-regulated (<em>P</em> < 0.05) in the EA group. 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引用次数: 0

摘要

目的探讨电针（EA）对帕金森病（PD）小鼠血脑屏障通透性及基质金属蛋白酶（MMPs）的调节作用。方法48只C57BL/6小鼠随机分为正常对照组（NC）、PD模型组（PD）、EA组和EA + SB-3CT抑制剂组（EA + SB-3CT），每组12只。本实验采用鱼藤酮灌胃法（IG）建立PD模型，PD组、EA组和EA+SB-3CT组持续灌胃4周。EA + SB-3CT组，鱼藤酮IG 1 h后，腹腔注射MMP-2/9抑制剂SB-3CT （25 mg/kg/d）。造模成功后，EA组和EA + SB-3CT组分别在“风阜（GV16）”和双侧“太中（LR3）”、“足三里（ST36）”处进行电激，每次1 mA、2 Hz，每次30 min，每天1次，连续2周。采用开野法观察各组小鼠行为变化，免疫组化法检测黑质中酪氨酸羟化酶（TH）水平，Evans蓝染色法检测血脑屏障通透性，Western blotting法检测黑质中ZO-1、ocludin、cludin -1、MMP-2、MMP-9蛋白表达。结果与NC组比较，行为评分明显升高(P <；总运动时间、总距离和平均速度降低(P <；PD组差异无统计学意义（0.05）。黑质中TH的表达降低(P <；0.05)，脑组织Evans蓝水平升高(P <；0.05)， ZO-1、occludin、claudin-1蛋白表达较低(P <；0.05)，而MMP-2和MMP-9的表达较高(P <；PD组差异无统计学意义（0.05）。与PD组比较，行为评分降低(P <；0.05)，总运动时间、总距离和平均速度增加(P <；0.05)。此外，黑质中TH表达升高(P <；0.05)，脑组织Evans蓝水平较低(P <；0.05)， ZO-1、occludin和claudin-1蛋白表达上调(P <；0.05)， MMP-2和MMP-9表达下调(P <；0.05)。与EA组比较，Evans blue水平降低(P <；0.05)， ZO-1和occludin蛋白表达上调(P <；0.05)， MMP-2和MMP-9表达进一步下调(P <；EA+SB-3CT组差异无统计学意义（0.05）。结论ea能有效改善PD小鼠运动功能障碍，减轻多巴胺能神经元损伤，发挥神经保护作用。EA通过上调紧密连接蛋白、ZO-1、occludin的表达，下调基质金属结合酶、MMP-2、MMP-9的表达，有效改善PD小鼠血脑屏障通透性。EA的神经保护作用可能是通过MMP-2/9通路介导的血脑屏障通透性的改善而获得的。

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Effect of electroacupuncture on the MMP-2/9 pathway mediated blood-brain barrier permeability in mice with Parkinson's disease

Objective

To investigate the effects of electroacupuncture (EA) on the blood-brain barrier permeability and the regulation of matrix metalloproteinases (MMPs) in the mice with Parkinson's disease (PD).

Methods

Forty-eight C57BL/6 mice were randomly assigned into the normal control (NC) group, the PD model (PD) group, the EA group and the EA + SB-3CT inhibitor group (EA + SB-3CT), with 12 mice in each group. In this experiment, the PD model was established by intragastric administration (IG) with rotenone for 4 wk in the PD group, EA group and EA+SB-3CT group. In the EA + SB-3CT group, 1 h after IG with rotenone, the mice were intraperitoneally injected with MMP-2/9 inhibitor, SB-3CT (25 mg/kg/d). After successfully modeled, in the EA group and EA + SB-3CT group, EA was conducted at “Fengfu (GV16)” and bilateral “Taichong (LR3)” and “Zusanli (ST36)”, at 1 mA and 2 Hz for 30 min each time, once a day, for consecutive 2 wk. The behavioral changes of the mice were observed in each group using the open field test, the level of tyrosine hydroxylase (TH) in the substantia nigra was determined by immunohistochemistry, the permeability of the blood-brain barrier was detected by Evans blue staining, and the protein expression of ZO-1, ocludin, claudin-1, MMP-2 and MMP-9 in the substantia nigra was detected by Western blotting.

Results

Compared with the NC group, the behavioral scores increased (P < 0.05), while total time of locomotion, total distance and average speed were reduced (P < 0.05) in the PD group. The expression of TH in the substantia nigra decreased (P < 0.05), Evans blue level in the brain tissue increased (P < 0.05), and the protein expression of ZO-1, occludin and claudin-1 was lower (P < 0.05), whereas MMP-2 and MMP-9 expression was higher (P < 0.05) in the PD group. Compared with the PD group, behavioral scores decreased (P < 0.05), while the total time of locomotion, total distance and average speed increased (P < 0.05) in the EA group. Additionally, TH expression in the substantia nigra was elevated (P < 0.05), Evans blue level in the brain tissue was lower (P < 0.05), the protein expression of ZO-1, occludin and claudin-1 was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was down-regulated (P < 0.05) in the EA group. Compared with the EA group, Evans blue level was reduced (P < 0.05), the protein expression of ZO-1 and occludin was up-regulated (P < 0.05), and MMP-2 and MMP-9 expression was further down-regulated (P < 0.05) in the EA+SB-3CT group.

Conclusion

EA can effectively ameliorate the motor dysfunction of PD mice, reduce the damage of dopaminergic neurons, and play a neuroprotective role. EA can effectively improve the blood–brain barrier permeability in PD mice by up-regulating the expression of tight junction proteins, ZO-1 and occludin, and down-regulating the expression of matrix metalloporteinases, MMP-2 and MMP-9. The neuroprotective role of EA may be obtained by improving the blood-brain barrier permeability mediated by MMP-2/9 pathway.

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来源期刊

World Journal of Acupuncture-Moxibustion INTEGRATIVE & COMPLEMENTARY MEDICINE-

CiteScore

1.30

自引率

28.60%

发文量

1089

审稿时长

50 days

期刊介绍： The focus of the journal includes, but is not confined to, clinical research, summaries of clinical experiences, experimental research and clinical reports on needling techniques, moxibustion techniques, acupuncture analgesia and acupuncture anesthesia.