基于TMT定量蛋白质组学探讨“黄芪-黄连”药对干预IGT大鼠的作用靶点及信号通路的研究  

Research on the Target and Signal Pathway of"Astragalus membranaceus-Coptis chinensis"in the Treatment of IGT Rats Based on TMT Quantitative Proteomics

作　　者：李捷 郑雅峰 徐云生[2] LI Jie;ZHENG Ya-feng;XU Yun-sheng(Second Clinical Medical College of Shandong University of Traditional Chinese Medicine,Ji'nan,Shandong 250014,China;Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Ji'nan,Shandong 250001,China)

机构地区：[1]山东中医药大学第二临床医学院,山东济南250014 [2]山东中医药大学第二附属医院,山东济南250001

出　　处：《时珍国医国药》2023年第3期751-755,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金面上项目(81673966);泰山学者专项资助项目(ts201712097)。

摘　　要：目的基于串联质谱标签(TMT)蛋白质组学技术,探究“黄芪-黄连”对糖耐量减低(IGT)大鼠的潜在治疗靶点,探索该药对抗IGT的生物学机制。方法SPF级Wistar雄性大鼠,随机分成空白组(n=10),IGT模型组(n=10),“黄芪-黄连”组(n=9),药对组给予中药混悬液4.69g·kg^(-1)·d^(-1)。干预8周后,检测血糖相关指标及胰腺组织β/α细胞分布。应用蛋白质组学技术明确三组胰腺组织具有差异表达的蛋白质靶点,取(模型组/空白组)差异表达靶蛋白与(药对组/模型组)的靶蛋白的交集并作生物学富集功能分析。结果“黄芪-黄连”可减轻IGT大鼠糖负荷后2h血糖(P<0.05),并可有效改善胰岛β/α细胞分布。蛋白质组学结果显示,根据差异倍数及P值,“黄芪-黄连”干预IGT的治疗靶点有83个(Flot2、Azgp1、Lpcat3等),其中上调的有12个,下调的71个。KEGG富集功能分析结果显示,“黄芪-黄连”参与甘油磷脂代谢、mTOR、PPAR等多条信号通路来治疗IGT。结论“黄芪-黄连”干预IGT过程中具有多成分-多靶点-多通路的特征,可能通过调控83个蛋白靶点,参与甘油磷脂代谢等多条信号途径来发挥抗IGT作用。该研究为进一步探讨“黄芪-黄连”治疗IGT的作用机制提供了依据和方向。Objective Based on Tandem Mass Tags(TMT)proteomics technology,this study aims to explore the potential therapeutic targets of"Astragalus membranaceus-Coptis chinensis"on impaired glucose tolerance(IGT)rats,as well as the biological mechanism of this paired drugs against IGT.Methods SPF Wistar male rats were randomly divided into blank group(n=10),IGT model group(n=10),"Astragalus membranaceus-Coptis chinensis"group(n=9)."Astragalus membranaceus-Coptis chinensis"group was given Chinese herbal medicine suspension 4.69 g·kg^(-1)·d^(-1).After intervention for 8 weeks,blood glucose related indexes and distribution ofβ/αcells in pancreatic tissue were detected.Proteomics techniques were used to identify the differentially expressed protein targets in three groups of pancreatic tissues.The intersection of differentially expressed target proteins(model group/blank group)and target proteins(drug pair group/model group)was taken,and the biological en-richment function analysis was carried out.Results"Astragalus membranaceus-Coptis chinensis"could reduce the blood glucose of IGT rats at 2h after glucose loading(P<0.05),and effectively improve the distribution of isletβ/αcells.Proteomic results showed that according to the fold change and P value,there were 83 therapeutic target proteins(Flot2,Azgp1,Lpcat3,etc.)in IGT rats interfered with"Astragalus membranaceus-Coptis chinensis",among which 12 were up-regulated and 71 were down-regulated.The results of KEGG enrichment function analysis showed that"Astragalus membranaceus-Coptis chinensis"participated in glycerol phospholipid metabolism,mTOR,PPAR and other signaling pathways in the treatment of IGT.Conclusion"Astragalus membranaceus-Coptis chinensis"has the characteristics of multi-component,multi-target and multi-pathway in the process of IGT intervention,which may play an anti-IGT role by regulating 83 protein targets and participating in glycerol and phospholipid metabolism and other signal pathways.This study provides a basis and direction for further exploring the

关 键 词：黄芪 黄连 糖耐量减低 蛋白质组学 靶蛋白 

分 类 号：R2-03[医药卫生—中医学]