小麦肽对小鼠成肌细胞C2C12凋亡的影响及机制研究  

Effects of Wheat Peptides on Inhibition of Apoptosis of Mouse C2C12 Myoblasts and Mechanism Study

作　　者：夏羽菡[1] 丁欢[2] 孟甘露 赵荣[4] 刘文颖 杜颖鑫 XIA Yu-han;DING Huan;MENG Gan-lu;ZHAO Rong;LIU Wen-ying;DU Ying-xin(Clinical Nutrition Department,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Intensive Care Unit,General Hospital of Ningxia Medical University,Yinchuan 750004,China;Beijing Engineering Research Center of Protein&Functional Peptides/China National Research Institute of Food and Fermentation Industries,Beijing 100015,China;Outpatient Department,General Hospital of Ningxia Medical University,Yinchuan750004,China)

机构地区：[1]宁夏医科大学总医院临床营养科,银川750004 [2]宁夏医科大学总医院重症医学科,银川750004 [3]中国食品发酵工业研究院有限公司/北京市蛋白功能肽工程技术研究中心,北京100015 [4]宁夏医科大学总医院门诊部,银川750004

出　　处：《中国食物与营养》2024年第10期54-61,共8页Food and Nutrition in China

基　　金：宁夏重点研发计划项目“COPD型营养产品的研发与临床营养干预效应评价”(项目编号:2021BEG02027);宁夏重点研发计划项目“早期强化蛋白短肽制剂联合康复运动精准治疗ICU获得性肌无力的研究”(项目编号:2022BEG03125)。

摘　　要：目的:采用小鼠成肌细胞C2C12探究小麦肽对其增殖和凋亡的影响,并探明可能的作用机制。方法:CCK-8法检测小麦肽组C2C12和对照组C2C12的增殖和凋亡指数,采用高通量转录组测序进行差异表达分析,通过STRING分析构建差异基因的蛋白-蛋白相互作用(PPI)网络,经Cytoscape可视化,探究C2C12中受小麦肽影响的潜在靶标基因及其功能。结果:5mg/mL小麦肽组抑制细胞凋亡较对照组差异显著(T>1.67,P<0.05)。相较对照组,小麦肽组C2C12中鉴定出370个差异基因,上调基因表达109个、下调基因表达261个,FC≥3/2or≤2/3。经分析,上调基因表达主要富集于炎症响应、免疫响应、TNF信号通路和IL-17信号通路等相关通路,下调基因表达主要富集于氧化还原过程等相关通路,PPI互作参数interactionscore≥0.7。从PPI的差异基因中得到前10个hub基因,并筛选到趋化因子CXCL1、CCL5、CCL2、CXCL5、CXCR4、Il6、MMP3。经分析,hub基因倾向于在趋化因子介导的信号通路、细胞对趋化因子的反应和趋化因子的反应作为生物学过程方面富集,其中趋化因子CXCL1、CCL2、CCL5基因与C2C12相关。结论:本研究揭示小麦肽可促进C2C12增殖,抑制细胞凋亡。并且小麦肽通过调节CXCL1、CCL5、CCL2、CXCL5、CXCR4等趋化因子表达,抑制成肌细胞的凋亡。【Objective】Mouse skeletal muscle myoblasts(C2C12)were used to explore the effects of wheat peptides on proliferation and apoptosis.The possible mechanisms of action of the effects were also explored.【Method】Proliferation and apoptosis indices of wheat peptides groups C2C12 and control C2C12 by CCK-8 assay.Differential expression analysis using high-throughput transcriptome sequencing.STRING Analysis was used to construct PPI of differential Genes.Potential target genes in C2C12 affected by wheat peptides and their functions were explored by Cytoscape visualization.【Result】Compared with the control group,a significant difference in inhibition of apoptosis in the wheat peptides group at a dose of 5 mg/mL(T>1.67,P<0.05).Compared with controls,370 differential genes were identified in C2C12 of the wheat peptides group.Among them,109 were up-regulated gene expression and 261 were down-regulated gene expression,FC≥3/2 or≤2/3.Up-regulated genes were mainly enriched in the inflammatory response,immune response,TNF signaling pathway,and IL-17 signaling pathway.Down-regulated genes were enriched in redox processes and other related pathways,and the PPI interaction score is≥0.7.The top 10 hub genes were obtained from the differential genes of PPI.After reconstructing the interactions network,the chemokines CXCL1,CCL5,CCL2,CXCL5,CXCR4,Il6,and MMP3 were jointly screened.After analysis,the hub genes tend to be enriched in"chemokine-mediated signaling pathways","cellular response to chemokines"and"chemokine response"as biological processes.The chemokine CXCL1,CCL2,and CCL5 genes were associated with C2C12.【Conclusion】This study reveals that wheat peptides promote C2C12 proliferation and inhibit apoptosis.Moreover,wheat peptides inhibit apoptosis of myofibroblasts by regulating the expression of chemokines such as CXCL1,CCL5,CCL2,CXCL5,and CXCR4.

关 键 词：小麦肽 小鼠骨骼肌成肌细胞C2C12 趋化因子 肌肉减少症 

分 类 号：R685[医药卫生—骨科学]