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血浆来源外泌体蛋白质组的生物信息学分析:急性期脊髓损伤患者中参与胆固醇代谢过程的外泌体

Bioinformatic Analysis of the Proteome in Exosomes Derived From Plasma: Exosomes Involved in Cholesterol Metabolism Process of Patients With Spinal Cord Injury in the Acute Phase.

作者信息

Wu Chunshuai, Yu Jinjuan, Xu Guanhua, Gao Hong, Sun Yue, Huang Jiayi, Sun Li, Zhang Xu, Cui Zhiming

机构信息

Department of Spine Surgery, Nantong First People's Hospital, The Affiliated Hospital 2 of Nantong University, Nantong, China.

Department of Administrative Office, The Third People's Hospital of Nantong, Nantong, China.

出版信息

Front Neuroinform. 2021 Jul 9;15:662967. doi: 10.3389/fninf.2021.662967. eCollection 2021.

Abstract

Spinal cord injury (SCI) is a common but severe disease caused by traffic accidents. Coronary atherosclerotic heart disease (CHD) caused by dyslipidemia is known as the leading cause of death in patients with SCI. However, the quantitative analysis showed that the cholesterol and lipoprotein concentrations in peripheral blood (PB) did not change significantly within 48 h after SCI. Due to the presence of the Blood spinal cord barrier (BSCB), there are only few studies concerning the plasma cholesterol metabolism in the acute phase of SCI. Exosomes have a smaller particle size, which enables them relatively less limitation of BSCB. This study uses exosomes derived from the plasma of 43 patients in the acute phase of SCI and 71 patients in the control group as samples. MS proteomics and bioinformatics analysis found 590 quantifiable proteins, in which 75 proteins were upregulated and 153 proteins were downregulated, and the top 10 differentially expressed proteins are those including downregulating proteins: HIST1H4A, HIST2H3A, HIST2H2BE, HCLS1, S100A9, HIST1H2BM, S100A8, CALM3, YWHAH, and SFN, and upregulating proteins: SERPIND1, C1QB, SPTLC3, IGHV4-28, C4A, IGHV4-38-2, IGHV4-30-2, SLC15A1, C4B, and ACTG2. Enrichment analysis showed that the largest part of proteins was related to cholesterol metabolism among the downregulated proteins. The main components of cholesterol [ApoB-48 and ApoB-100 increased, ApoA-I, ApoA-II, ApoA-IV, ApoC, ApoE, and Apo(a) decreased] were changed in exosomes derived from plasma of patients. ELISA analysis showed that some components were disordered in the acute phase of SCI. These results suggested that the exosomes might be involved in cholesterol metabolism regulation in the acute phase of SCI.

摘要

脊髓损伤(SCI)是一种由交通事故导致的常见但严重的疾病。血脂异常引起的冠状动脉粥样硬化性心脏病(CHD)是SCI患者的主要死因。然而,定量分析表明,SCI后48小时内外周血(PB)中的胆固醇和脂蛋白浓度没有显著变化。由于血脊髓屏障(BSCB)的存在,关于SCI急性期血浆胆固醇代谢的研究较少。外泌体的粒径较小,因此相对较少受到BSCB的限制。本研究以43例SCI急性期患者和71例对照组患者血浆来源的外泌体为样本。通过质谱蛋白质组学和生物信息学分析发现了590种可定量的蛋白质,其中75种蛋白质上调,153种蛋白质下调,差异表达前10的蛋白质包括下调蛋白:HIST1H4A、HIST2H3A、HIST2H2BE、HCLS1、S100A9、HIST1H2BM、S100A8、CALM3、YWHAH和SFN,以及上调蛋白:SERPIND1、C1QB、SPTLC3、IGHV4-28、C4A、IGHV4-38-2、IGHV4-3o-2、SLC15A1、C4B和ACTG2。富集分析表明,下调蛋白中最大部分与胆固醇代谢相关。患者血浆来源外泌体中胆固醇的主要成分(ApoB-48和ApoB-100增加,ApoA-I、ApoA-II、ApoA-IV、ApoC、ApoE和Apo(a)减少)发生了变化。ELISA分析表明,SCI急性期某些成分紊乱。这些结果提示,外泌体可能参与SCI急性期的胆固醇代谢调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fcc/8299276/e24d184a4ca0/fninf-15-662967-g0001.jpg

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