[电针对SAMP8小鼠肌肉和脑运动功能和PGC-1α/FNDC5/BDNF通路的影响]

摘要(中文译文)

观察电针对SAMP8小鼠运动功能及骨骼肌形态的影响，并从过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC-1α）/Ⅲ型纤连蛋白结构域蛋白5（FNDC5）/脑源性神经营养因子（BDNF）通路探讨电针改善阿尔茨海默病运动功能障碍的机制。将SAMP8小鼠随机分为模型组和电针组，每组9只，另取9只抗衰老SAMR1小鼠作为对照组。电针组取“百会”“大椎”“肾俞”电针20 min，每日1次，8 d为1个疗程，疗程间休息2 d，共治疗3个疗程。采用抓握实验、游泳实验、悬吊实验和后肢夹持实验检测小鼠运动功能；HE染色观察腓肠肌形态结构；免疫组织化学染色观察腓肠肌PGC-1α、FNDC5、BDNF阳性表达；实时荧光定量PCR检测腓肠肌和大脑运动皮质PGC-1α、FNDC5、BDNF mRNA表达水平；Western blot检测腓肠肌和大脑运动皮质PGC-1α、FNDC5、BDNF蛋白表达水平。与对照组比较，模型组小鼠峰值抓力、平均游泳速度和最大游泳速度、悬吊实验评分均显著降低（<0.01），后肢夹持实验评分显著升高（<0.01）；腓肠肌肌纤维疏松、排列不规则，间距增宽，胞质染色不均；腓肠肌PGC-1α、FNDC5、BDNF阳性表达面积比显著降低（<0.01），腓肠肌和大脑运动皮质PGC-1α、FNDC5、BDNF mRNA及蛋白相对表达量均显著降低（<0.01）。与模型组比较，电针组小鼠峰值抓力、平均游泳速度和最大游泳速度、悬吊实验评分均显著升高（<0.01），后肢夹持实验评分显著降低（<0.01）；肌纤维完整、排列规则，间距变窄，胞质染色均匀；PGC-1α、FNDC5、BDNF阳性表达面积比显著升高（<0.01），腓肠肌和大脑运动皮质PGC-1α、FNDC5、BDNF mRNA及蛋白相对表达量均显著升高（<0.01，<0.05）。腓肠肌与大脑运动皮质PGC-1α、FNDC5、BDNF mRNA表达的相关性分析结果显示呈高度正相关（>0.70，<0.01）。电针可改善SAMP8小鼠运动功能障碍及骨骼肌形态，其机制可能与上调腓肠肌和大脑运动皮质PGC-1α、FNDC5、BDNF表达有关。

Abstract

To observe the effect of electroacupuncture (EA) on motor function and skeletal muscle morphology in SAMP8 mice, and to explore the mechanisms of EA improving motor dysfunction in Alzheimer's disease from the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α)/fibronectin type Ⅲ domain-containing protein 5 (FNDC5)/brain-derived neurotrophic factor (BDNF) pathway. SAMP8 mice were randomly divided into model and EA groups, with 9 mice in each group. Nine anti-aging SAMR1 mice were used as control group. In the EA group, "Baihui"(GV20), "Dazhui"(GV14) and "Shenshu"(BL23) were needled with EA for 20 min every day, 8 d as a course of treatment, with an interval of 2 d between courses. A total of 3 courses was proceeded. The motor function of mice was detected by grasping test, swimming test, suspension test and hind limb clamping test. The morphological structure of gastrocnemius muscle was observed by HE staining. The positive expressions of PGC-1α, FNDC5 and BDNF in gastrocnemius muscle were observed by immunohistochemical staining. The expression levels of PGC-1α, FNDC5 and BDNF mRNAs in gastrocnemius muscle and cerebral motor cortex were detected by real-time fluorescence quantitative PCR. The expression levels of PGC-1α, FNDC5 and BDNF proteins in gastrocnemius muscle and cerebral motor cortex were detected by Western blot. Compared with the control group, the peak grip strength, average and maximum swimming speed, and suspension test score of the model group were significantly decreased (<0.01), and the hind limb clamping test score was significantly increased (<0.01). The gastrocnemius muscle fibers were loose and irregularly arranged, the spacing was widened and the cytoplasmic staining was uneven. The positive expression area ratios of PGC-1α, FNDC5 and BDNF in gastrocnemius muscle were significantly decreased (<0.01), and the relative expression levels of PGC-1α, FNDC5 and BDNF mRNAs and proteins in gastrocnemius muscle and cerebral motor cortex were significantly decreased (<0.01). Compared with the model group, the peak grip strength, average and maximum swimming speed, and suspension test score of the EA group were significantly increased (<0.01), and the hind limb clamping test score was significantly decreased (<0.01). The muscle fibers were intact and arranged regularly, the spacing was narrowed, and the cytoplasmic staining was uniform.The positive expression area ratios of PGC-1α, FNDC5 and BDNF were significantly increased (<0.01), and the relative expression levels of PGC-1α, FNDC5 and BDNF mRNAs and proteins in gastrocnemius muscle and cerebral motor cortex were significantly increased (<0.01, <0.05). The correlation analysis results of PGC-1α, FNDC5 and BDNF mRNA expression in gastrocnemius and cerebral motor cortex showed a highly positive correlation (>0.70, <0.01). EA can improve motor dysfunction and skeletal muscle morphology in SAMP8 mice, and its mechanism may be related to up-regulation of PGC-1α, FNDC5 and BDNF expressions in gastrocnemius and cerebral motor cortex.

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