[Effect of electroacupuncture invention on activities of PGC-1α/Irisin (FNDC5)/BDNF signaling in cerebral cortex, hippocampus and muscles in focal cerebral ischemic/reperfusion injury rats]

Zhen Ci Yan Jiu. 2022 May 25;47(5):428-34. doi: 10.13702/j.1000-0607.20210495.
[Article in Chinese]

Abstract

Objective: To observe the effect of electroacupuncture(EA) on the expression of peroxisome proliferator-activated receptor gamma coactivators-1-alpha (PGC-1α), Irisin and brain-derived neurotrophic factor (BDNF) in the ischemic peripheral cortex, hippocampus and local skeletal muscle in rats with focal cerebral ischemic/reperfusion injury (CI/RI), so as to explore its underlying mechanism of improving of CI/RI.

Methods: Male SD rats were randomly divided into 3 groups: sham-operation, model and EA (11 rats in each group). The focal CI/RI model was established by middle cerebral artery occlusion (MCAO). EA (2 Hz /15 Hz, 2 to 4 mA) was applied to "Quchi" (LI11) and "Zusanli" (ST36) of the affected side for 20 min, once a day for 7 days. Zea-Longa's score and Balance Beam score were used to evaluate the neurological and motor functions. The infarcted volume of the brain was detected by using 2,3,5-triphenyltetrazolium chloride staining. The expression levels of PGC-1α, fibronectin type III domain-containing protein 5(FNDC5) and BDNF proteins in the ischemic peripheral cortex, hippocampus and local skeletal muscle were detected by Western blot.

Results: Compared with the sham-operation group, the Zea-Longa's score, Balance Beam score, percentage of cerebral infarct volume were notably increased (P<0.01), while the expression levels of PGC-1α, FNDC5 and BDNF proteins in the cerebral cortex and hippocampus (not in the local muscle) were significantly down-regulated in the model group (P<0.01, P<0.05). In comparison with the model group, the increase of Zea-Longa's score, Balance Beam score, percentage of cerebral infarct volume, and the decrease of expression levels of PGC-1α, FNDC5 and BDNF proteins in the ischemic peripheral cortex and that of BDNF in the hippocampus were reversed in the EA group (P<0.01, P<0.05). No significant changes were found in the expression levels of hippocampal PGC-1α and FNDC5 proteins in the hippocampus and those of PGC-1α, FNDC5 and BDNF proteins in the local muscle after EA intervention (P>0.05).

Conclusion: EA can improve neurological and motor functions and reduce cerebral infarction volume in CI/RI rats, which may be related to its functions in activating PGC-1α/Irisin(FNDC5)/BDNF pathway in the cerebral cortex.

目的:观察电针对局灶性脑缺血再灌注损伤大鼠缺血周边区皮层、海马及电针部位骨骼肌中过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)、鸢尾素(Irisin)、脑源性神经营养因子(BDNF)表达的影响, 探讨电针改善脑缺血再灌注损伤的潜在机制。方法:SD大鼠随机分为假手术组、模型组、电针组, 每组11只。采用线栓法建立局灶性大脑中动脉阻塞大鼠模型。电针组电针患侧“曲池”“足三里”, 1次/d, 每次20 min, 共7 d。采用Longa评分及平衡木评分观察各组大鼠神经及运动功能损伤情况, 2, 3, 5-三苯基氯化四氮唑染色法检测各组大鼠脑梗死体积, Western blot法检测大鼠缺血周边区皮层、海马及电针部位骨骼肌PGC-1α、Ⅲ型纤连蛋白域包含蛋白5(FNDC5)和BDNF的表达水平。结果:与假手术组比较, 模型组大鼠Longa评分及平衡木评分升高(P<0.01), 脑梗死体积百分比明显升高(P<0.01), 缺血周边区皮层及海马PGC-1α、FNDC5、BDNF的表达均明显降低(P<0.01, P<0.05), 骨骼肌PGC-1α、FNDC5、BDNF的表达无明显变化(P>0.05);与模型组比较, 电针组大鼠Longa评分及平衡木评分显著降低(P<0.01), 脑梗死体积百分比明显降低(P<0.01), 缺血周边区皮层PGC-1α、FNDC5、BDNF蛋白表达显著升高(P<0.01), 同侧海马仅BDNF蛋白表达显著升高(P<0.05), 同侧海马PGC-1α、FNDC5和骨骼肌PGC-1α、FNDC5、BDNF蛋白表达均无明显变化(P>0.05)。结论:电针可以改善脑缺血再灌注损伤大鼠运动功能, 减小脑梗死体积, 其机制可能与电针激活皮层PGC-1α/Irisin(FNDC5)/BDNF通路相关。.

Keywords: Brain-derived neurotrophic factor; Cerebral ischemic/reperfusion injury; Electroacupuncture; Irisin; Peroxisome proliferator-activated receptor gamma coactivators-1-alpha.

MeSH terms

  • Animals
  • Brain Injuries*
  • Brain Ischemia* / surgery
  • Brain Ischemia* / therapy
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cerebral Cortex / metabolism
  • Electroacupuncture*
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Hippocampus / metabolism
  • Infarction, Middle Cerebral Artery
  • Inventions
  • Male
  • Muscle, Skeletal / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury* / genetics
  • Reperfusion Injury* / metabolism
  • Reperfusion Injury* / therapy

Substances

  • Brain-Derived Neurotrophic Factor
  • FNDC5 protein, rat
  • Fibronectins
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha