黄芪多糖减轻糖尿病性肌少症大鼠肌肉萎缩的作用机制研究

Study on the mechanism of Astragalus polysaccharide alleviating muscle atrophy in diabetic sarcopenia rats

[目的]探究黄芪多糖通过作用于磷脂酰肌醇3激酶(PI3K)-蛋白激酶B(AKT)-叉头框转录因子O亚族1(FOXO1)信号通路及相关炎症因子对糖尿病性肌少症大鼠肌肉萎缩的改善及治疗作用。[方法]一次性链脲佐菌素腹腔注射构造糖尿病动物模型,随机分为模型组、黄芪多糖组和二甲双胍组,另设置无干预正常组,分组给药3个月,实验结束后进行腓肠肌苏木精-伊红(HE)染色;蛋白质免疫印迹法(Western Blot)测定磷酸化蛋白激酶B(P-AKT)/AKT及FOXO1蛋白含量;实时荧光定量聚合酶链反应(qPCR)检测白细胞介素(IL-6)、抑癌基因TP53、热休克转录因子1(HSF1)、基质金属蛋白酶-9(MMP-9)水平;检测血清生化指标三酰甘油(TG)。[结果]与模型组相比,黄芪多糖组腓肠肌肌细胞明显改善,细胞体积变大、间隙变窄,炎性渗出显著减轻;另外,黄芪多糖组的糖尿病保护因子P-AKT/AKT、FOXO1蛋白含量明显上升;炎性因子IL-6、TP53、HSF1及MMP-9含量明显下降。在血脂方面,西药二甲双胍组TG下降更加明显。[结论]黄芪多糖可能通过PI3K-AKT-FOXO1信号通路,降低IL-6、TP53炎性因子水平,影响HSF1和MMP-9的活性,从而改善糖尿病性肌少症大鼠的肌肉萎缩。

[Objective]To explore the therapeutic effect of Astragalus polysaccharide(APS)on muscle atrophy in diabetic sarcopenia rats by acting on PI3K-AKT-FOXO1 signaling pathway and related inflammatory factors.[Methods]The diabetic animal model was constructed by one-time intraperitoneal injection of streptozotocin,and was randomly divided into model group,APS group and metformin group.After the experiment,HE staining and Western Blot were used to determine P-AKT/AKT and FOXO1 protein content in gastnemius muscle,and fluorescence quantitative qPCR was used to detect IL-6,TP53,HSF1,MMP-9 and serum biochemical index TG.[Results]Compared with model group,the muscle cells of gastrocnemius muscle in APS group were significantly improved,the cell volume was enlarged,the space was narrowed,and the inflammatory exudation was significantly reduced.In addition,the levels of P-AKT/AKT and FOXO1 protein were significantly increased in the APS group.The contents of inflammatory factor IL-6,TP53,heat shock transcription factor 1 and matrix metalloproteinase 9 decreased significantly.In terms of blood lipid,triglyceride decreased more significantly in the metformin group.[Conclusion]APS may reduce the levels of IL-6 and TP53 inflammatory factors through PI3K-AKT-FOXO1 signaling pathway,affect the activities of heat shock transcription factor 1 and matrix metalloprotein-9,and thus improve the muscle atrophy in diabetic sarcosis rats.