MRb1对高脂饮食联合链脲佐菌素诱导的2型糖尿病小鼠骨骼肌蛋白质组学分析

Proteomics Analysis of MRb1 on Skeletal Muscle in Type 2 Diabetic Mice Induced by High-fat Diet Combined with Streptozotocin

探究丙二酰基人参皂苷Rb1(MRb_(1))对2型糖尿病小鼠的治疗作用,并通过骨骼肌蛋白质组学技术研究其作用机制。试验选取C57BL/6J小鼠作为研究对象,采用高脂饮食联合链脲佐菌素建立2型糖尿病小鼠模型。设立正常组(NC)、模型组(DC)、MRb_(1)高剂量组(MRb_(1)-40)和MRb_(1)低剂量组(MRb_(1)-20),每组10只小鼠。给药组小鼠分别给予40 mg/(kg·d)及20 mg/(kg·d)剂量的MRb_(1),进行为期5周的治疗。试验结果显示,MRb_(1)能显著降低2型糖尿病小鼠空腹血糖、血脂和胰岛素指数,升高了胰岛素的水平,改善了胰岛素抵抗和脂质代谢紊乱。同时,骨骼肌蛋白质组学研究结果显示,NC与DC比较组共筛选出差异表达蛋白108个,其中上调蛋白有62个,下调蛋白有46个。差异蛋白富集的KEGG信号通路主要包括PPAR信号通路、脂肪酸降解、脂肪酸代谢、胰岛素信号通路、AMPK信号通路等。DC与MRb_(1)比较组共筛选出差异表达蛋白48个,其中上调蛋白有39个,下调蛋白有9个。差异蛋白富集的KEGG信号通路主要有糖酵解、糖异生、胰高血糖素信号通路、钙信号通路等。结果表明:MRb_(1)显著地改变了糖尿病小鼠骨骼肌组织中蛋白质表达谱,影响多条与糖尿病和骨骼肌相关的信号通路,为糖尿病骨骼肌相关发病机制和MRb_(1)治疗2型糖尿病的靶点筛选提供参考。

The purpose of this study was to explore the therapeutic effect of malonyl ginsenoside MRb_(1) on type 2 diabetic mice,and to further study its action mechanism through the analysis of skeletal muscle proteomics.In the experiment,C57BL/6J mice were selected as the research object,and type 2 diabetes mouse model was established by high-fat diet combined with streptozotocin.Normal group(NC),model group(DC),MRb_(1) high dose group(MRb_(1)-40)and MRb_(1) low dose group(MRb_(1)-20)were set up,with 10 rats in each group.During the experiment,mice in the high-dose and low-dose MRb_(1) groups were given a 40 mg/(kg·d)and 20 mg/(kg·d)MRb_(1) for 5 weeks.The results showed that MRb_(1) could significantly reduce fasting blood glucose,blood lipid levels and homeostatic model assessment-insulin resistance indexes,increased serum insulin levels and alleviate insulin resistance and hyperlipemia in type 2 diabetic mice.Meanwhile,the results of skeletal muscle proteomics showed that 108 differentially expressed proteins were screened between NC group and DC group,including 62 up-regulated proteins and 46 down-regulated proteins.The KEGG signaling pathways enriched by differentially expressed proteins mainly include PPAR signaling pathway,fatty acid degradation,fatty acid metabolism,insulin signaling pathway,AMPK signaling pathway,and so on.In addition,a total of 48 differentially expressed proteins were screened between DC group and MRb_(1) group,of which 39 were up-regulated and 9 were down-regulated.The KEGG signaling pathways enriched by differentially expressed proteins mainly include glycolysis,gluconeogenesis,glucagon signaling pathway,calcium signaling pathway,and so on.These results showed that the administration of MRb_(1) significantly alters protein expression profile in the skeletal muscle of diabetic mice and affects multiple signaling pathways closely related to diabetes and skeletal muscle.This study provides a reference for the screening of diabetic skeletal muscle-related pathogenesis and therapeutic targets.