气虚血瘀型腰椎管狭窄症患者增生肥厚与正常黄韧带之间的蛋白质表达差异  

Differential protein expression analysis of hypertrophic and normal ligamentum flavum in patients with lumbar spinal stenosis with Qi deficiency and blood stasis

作　　者：王梦抒 张宇[2] 郑周杭 陈龙 尤冬春 郭伟锋 胡飞 陈欢 刘幸明 吴荣海 张寅 Wang Mengshu;Zhang Yu;Zheng Zhouhang;Chen Long;You Dongchun;Guo Weifeng;Hu Fei;Chen Huan;Liu Xingming;Wu Ronghai;Zhang Yin(Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China;Guangdong Second Hospital of Traditional Chinese Medicine,Guangzhou 510095,Guangdong Province,China)

机构地区：[1]广州中医药大学,广东省广州市510405 [2]广东省第二中医院,广东省广州市510095

出　　处：《中国组织工程研究》2023年第35期5589-5595,共7页Chinese Journal of Tissue Engineering Research

基　　金：广东省自然科学基金项目-面上项目(2021A1515011723),项目负责人:张宇。

摘　　要：背景:从西医的病理机制来看,黄韧带增生肥厚是腰椎管狭窄症的关键致病因素,目前缺乏气虚血瘀型腰椎管狭窄症的生物学信息。目的:分析气虚血瘀型腰椎管狭窄症患者增生肥厚黄韧带与同证患者正常黄韧带之间的蛋白质表达差异。方法:选择2022年2-8月广东省第二中医院(黄埔医院)收治的气虚血瘀型腰椎管狭窄症患者6例,其中黄韧带增生肥厚者3例(实验组),黄韧带厚度正常者3例(对照组),采集所有患者黄韧带组织标本,进行4D Label free定量蛋白组学检测,筛选差异蛋白,运用GO、KEGG进行富集分析。结果与结论:①实验组与对照组表达差异的蛋白总数为183个,其中上调蛋白87个,下调蛋白96个;②表达差异蛋白的GO富集分析显示,生物进程主要集中在细胞进程、生物调节、对刺激的反应等;细胞组成则集中在细胞、细胞内、蛋白质复合物种;分子功能主要为连接、催化活性、分子功能调节剂等;③上调蛋白主要富集到溶酶体信号通路、类风湿性关节炎信号通路、金黄色葡萄球菌感染信号通路;下调蛋白共富集到8条信号通路,分别为p53信号通路、肾细胞癌信号通路、转化生长因子β信号通路、泛素介导的蛋白水解作用信号通路、Ca信号通路、cGMP-PKG信号通路、缺氧诱导因子1信号通路、癌症中蛋白聚糖信号通路;④实验组的重要差异蛋白有INHBA、MMP14、TNC、HTRA1、FGF2等;⑤气虚血瘀型腰椎管狭窄症患者增生肥厚黄韧带与同证患者正常黄韧带蛋白质表达存在差异,其中INHBA可能为该疾病的关键影响因子,其作用机制可能为激活转化生长因子β/Smad相关信号通路引起黄韧带增生肥厚,导致腰椎管狭窄症。BACKGROUND:From the pathological mechanism of Western medicine,ligamentum flavum hypertrophy is the key pathogenic factor of lumbar spinal stenosis,and there is a lack of biological information on lumbar spinal stenosis of the Qi deficiency and blood stasis type.OBJECTIVE:To analyze and compare differential protein expression between hypertrophic and normal ligamentum flavum in patients with lumbar spinal stenosis of the Qi deficiency and blood stasis type.METHODS:Ligamentum flavum tissue samples were collected from six lumbar spinal stenosis patients with Qi deficiency and blood stasis,including three cases of ligamentum flavum hypertrophy(experimental group)and three cases of normal ligamentum flavum(control group).4D Label free quantitative proteomic detection was performed to screen differentially expressed proteins.Gene oncology and Kyoto Encyclopedia of Genes and Genomes were used for enrichment analysis.RESULTS AND CONCLUSION:There were 183 differentially expressed proteins between the two groups,including 87 up-regulated and 96 down-regulated.Gene oncology enrichment analysis showed that biological processes mainly focused on cell processes,biological regulation and response to stimuli.Cell composition was concentrated in cell,intracellular,and protein-complex species.The main molecular functions included linkage,catalytic activity and molecular function regulator.The up-regulated proteins were mainly enriched to lysosomal signaling pathway,rheumatoid arthritis signaling pathway,and Staphylococcus aureus infection signaling pathway,while the down-regulated proteins were enriched to eight signaling pathways,namely p53 signaling pathway,renal cell carcinoma signaling pathway,transforming growth factorβsignaling pathway,ubiquitin-mediated protein hydrolysis signaling pathway,Ca signaling pathway,cGMP-PKG signaling pathway,hypoxia-inducible factor 1 signaling pathway,and proteoglycan signaling pathway in cancer.INHBA,MMP14,TNC,HTRA1,FGF2 were the important differentially expressed proteins in the experimenta

关 键 词：差异蛋白质 气虚血瘀证 腰椎管狭窄 黄韧带增生肥厚 INHBA MMP14 TNC HTRA1 FGF2 

分 类 号：R459.9[医药卫生—治疗学] R34[医药卫生—临床医学] R274