FoXO3a通路调控失神经肌萎缩的作用机制及银杏叶提取物的治疗作用

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目的观察银杏叶提取物(EGB761)在实验性大鼠失神经肌萎缩中的治疗效果,探讨银杏叶提取物对大鼠腓肠肌细胞中FoxO3a/MAFbx信号通路的影响。方法选用成年雌性Wistar大鼠54只,每组6只,切断右侧坐骨神经随机分为失神经组(30只)和药物干预组(24只),药物干预组每日银杏叶提取物(100mg/Kg体重)灌胃,在去神经第0、2、7、14、28d分别处死大鼠取其两侧腓肠肌。称肌湿重求出肌湿重比;以WEST BLOT检测右腓肠肌标本中p-FoxO3aS253、FoxO3a、MAFbx蛋白的表达量;RT-PCR检测FoxO3a、MAFbXmRNA的表达量。结果药物干预组各组肌湿重比比失神经组高,差异具有统计学意义(P<0.05)。药物干预组FoxO3a基因表达和蛋白表达较失神经组减少,在7、14、28d差异具有统计学意义(P<0.05)。药物干预后p-FoxO3aS253的磷酸化水平显著高于同期失神经组。药物干预组MAFbx基因和蛋白表达较失神经组下降,在第7、14、28d差异具有统计学意义(P<0.05)。结论大鼠失神经骨骼肌萎缩早期,银杏叶提取物可能是通过FoxO3a通路来防治失神经早期的骨骼肌萎缩。 Objective To observe the therapeutic effect of Ginkgo biloba extract (EGB761) on denervated muscular atrophy in rats and to explore the effect of Ginkgo biloba extract on FoxO3a / MAFbx signaling pathway in rat gastrocnemius cells. Methods Fifty-four adult female Wistar rats were randomly divided into three groups: denervated group (n = 30) and drug intervention group (n = 24) Kg body weight) were given intragastrically. Rats were sacrificed at 0, 2, 7, 14 and 28 days after denervation respectively. Weigh muscle wet weight to find out the ratio of muscle wet weight. The expression of p-FoxO3aS253, FoxO3a and MAFbx in right gastrocnemius muscle was detected by western blotting. The expression of FoxO3a and MAFbXmRNA was detected by RT-PCR. Results The muscle wet weight of the intervention group was higher than that of the denervated group, the difference was statistically significant (P <0.05). The expression of FoxO3a gene and protein in the intervention group were lower than those in the denervated group, with statistical significance at 7, 14 and 28 days (P <0.05). The level of phosphorylation of p-FoxO3aS253 after drug intervention was significantly higher than that of the same period of denervation group. The expression of MAFbx gene and protein in drug intervention group was lower than that in the denervated group, and the difference was statistically significant at the 7th, 14th, 28th day (P <0.05). Conclusion In the early stage of denervated skeletal muscle atrophy in rats, Ginkgo biloba extract may prevent skeletal muscle atrophy in early denervation through FoxO3a pathway.
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