电针对局灶性脑缺血再灌注大鼠过氧化物酶体增殖物激活受体γ辅激活因子1α、鸢尾素和脑源性神经营养因子的影响

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

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。

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-1αand 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.