基于血浆蛋白质组学与代谢组学技术探讨2型糖尿病气阴两虚证的生物学基础  

Study on biological basis of Qi and Yin deficiency syndrome in type 2 diabetes based on plasma proteomics and metabolomics

作　　者：高慧娟 冯兴中 GAO Hui-juan;FENG Xing-zhong(Tsinghua University Yuquan Hospital,Endocrine Immunology Department,Integrated Traditional Chinese and Western Medicine,Tsinghua University Hospital,Beijing 100040,China)

机构地区：[1]清华大学玉泉医院(清华大学中西医结合医院)内分泌科,北京100040

出　　处：《北京中医药》2024年第2期133-141,共9页Beijing Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金青年项目(82104812)。

摘　　要：目的 用血浆蛋白质组学与代谢组学技术分析2型糖尿病气阴两虚证的生物学基础。方法 选择2018年5月—2018年9月于首都医科大学附属北京世纪坛医院2型糖尿病气阴两虚证患者30例(Q组),2型糖尿病非气阴两虚证患者30例(F组),健康对照组30例(N组)。用Label free蛋白质组学方法对3组血浆样本进行差异蛋白分析,得到组间差异表达蛋白,采用KEGG pathway、String数据库对差异表达蛋白进行生物信息学分析;采用LC-MS联用技术对3组血浆样本进行差异代谢产物分析,用多维分析和单维分析相结合的方法筛选3组间差异代谢物,通过HMDB数据库进行搜库鉴定,并对筛选出的差异代谢物进行KEGG pathway分析,探索差异代谢物可能参与的代谢途径。结果 血浆蛋白质组学结果:在2型糖尿病组与健康对照组间筛选出差异蛋白119个,其中表达上调的有55个,表达下调的有64个;2型糖尿病气阴两虚证组与非气阴两虚证组间筛选出差异蛋白89个,其中表达上调的有51个,表达下调的有38个;2型糖尿病气阴两虚证组与非气阴两虚证组、健康对照组间筛选出差异表达蛋白18个,其中表达上调的有8个,表达下调的有10个。KEGG pathway分析发现PI3K-AKT信号通路、肾素分泌、IL-17等信号通路与2型糖尿病气阴两虚证的发生发展密切相关。血浆代谢组学结果:在2型糖尿病组与健康对照组间筛选出差异代谢产物32个。KEGG pathway分析发现支链氨基酸(BCAAs)合成与代谢途径、甘油磷脂代谢、丙氨酸、天冬氨酸和谷氨酸代谢途径可能与2型糖尿病的发生发展密切相关。进一步整合蛋白质组学与代谢组学结果发现,BCAAs代谢通路、PI3K-AKT信号通路均与2型糖尿病气阴两虚证密切相关。结论 血浆高水平的BCAAs可能通过抑制PI3K-AKT信号通路导致胰岛素信号通路受损,从而促进2型糖尿病气阴两虚证的发生发展。Objective To analyze the biological basis of qi and yin deficiency syndrome in type 2 diabetes by using proteomics and metabolomics technology.Methods From May 2018 to September 2018,30 cases of type 2 diabetes with qi-yin deficiency syndrome(group Q),30 cases of type 2 diabetes with non qi-yin deficiency syndrome(group F)and 30 cases of healthy control group(group N)were enrolled in Beijing Shijitan Hospital affiliated to the Capital Medical University.Label free proteomics method was used to analyze the differential proteins of three groups of plasma samples,and the differential expression proteins between groups were obtained.KEGG pathway and String database were used to analyze the bioinformatics of the differential expression proteins.LCMS combined technology was used to analyze differential metabolites in three groups of plasma samples.A combination of multidimensional analysis and single dimensional analysis was used to screen differential metabolites among the three groups.The HMDB database was searched and identified,and KEGG path analysis was performed on the screened differential metabolites to explore the metabolic pathways in which differential metabolites may participate.Results The results of plasma proteomics were that 119 differential proteins were screened between the type 2 diabetes group and the healthy control group,of which 55 were upregulated and 64 were down-regulated;89 differential proteins were screened out between type 2 diabetes with qi-yin deficiency syndrome and non qi-yin deficiency syndrome,among which 51 were up-regulated and 38 were down-regulated;18 differentially expressed proteins were screened out between the type 2 diabetes group with qi and yin deficiency syndrome,the non qi and yin deficiency syndrome group and the healthy control group,of which 8 were up-regulated and 10 were down-regulated.KEGG pathway analysis found that PI3K-AKT signaling pathway,renin secretion,IL-17 and other signaling pathways were closely related to the occurrence and development of qi-yin deficie

关 键 词：蛋白质组学 代谢组学 2型糖尿病 气阴两虚证 

分 类 号：R259[医药卫生—中西医结合]