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中华卫生应急电子杂志 ›› 2018, Vol. 04 ›› Issue (05) : 290 -297. doi: 10.3877/cma.j.issn.2095-9133.2018.05.005

所属专题: 文献

论著

SAA与脓毒症进程的相关性及其生物学意义
冯凯1, 郑燕华1, 杨鹤鸣2, 王奎1, 张刚1, 岳茂兴3, 尹进南4,()   
  1. 1. 100101 北京,解放军第306医院特种医学实验研究中心
    2. 100101 北京,解放军第306医院普通外科
    3. 100101 北京,解放军第306医院特种医学实验研究中心;213017 江苏常州,常州市武进人民医院急诊科
    4. 213017 江苏常州,常州市武进人民医院急诊科
  • 收稿日期:2018-07-10 出版日期:2018-10-18
  • 通信作者: 尹进南
  • 基金资助:
    江苏省常州市武进区科技局科研课题(WS201506)

Relationship between SAA and sepsis and its biological significance

Kai Feng1, Yanhua Zheng1, Heming Yang2, kui Wang1, Gang Zhang1, Maoxing Yue3, Jinnan Yin4,()   

  1. 1. Center for Special Medicine and Experimental Research, 306 Hospital of PLA, Beijing 100101, China
    2. General surgery, 306 Hospital of PLA, Beijing 100101, China
    3. Center for Special Medicine and Experimental Research, 306 Hospital of PLA, Beijing 100101, China; Department of Emergency, Changzhou Wujin People’s Hospital, Changzhou 213017, China
    4. Department of Emergency, Changzhou Wujin People’s Hospital, Changzhou 213017, China
  • Received:2018-07-10 Published:2018-10-18
  • Corresponding author: Jinnan Yin
  • About author:
    Corresponding author: Yin Jinnan, Email:
引用本文:

冯凯, 郑燕华, 杨鹤鸣, 王奎, 张刚, 岳茂兴, 尹进南. SAA与脓毒症进程的相关性及其生物学意义[J/OL]. 中华卫生应急电子杂志, 2018, 04(05): 290-297.

Kai Feng, Yanhua Zheng, Heming Yang, kui Wang, Gang Zhang, Maoxing Yue, Jinnan Yin. Relationship between SAA and sepsis and its biological significance[J/OL]. Chinese Journal of Hygiene Rescue(Electronic Edition), 2018, 04(05): 290-297.

目的

通过蛋白质组方法研究CLP模型小鼠,研究脓毒症进程相关的生物标志分子。

方法

85只小鼠,分成模型组和假手术组,制作小鼠CLP脓毒症模型,观察脓毒症发生发展的自然过程,同时在关键时间点采用iTRAQ法检测和鉴定血清蛋白,确定与脓毒症进程密切相关的关键分子,并通过qPCR法观察不同组织的mRNA表达,判断其组织来源。

结果

生存曲线显示,脓毒症小鼠发病12~32 h是死亡发生的关键时间,度过这一时间则进入自然康复期。同时发现一组蛋白在出现、高峰和恢复时间上与这一进程匹配。蛋白鉴定证实,这组蛋白包括SAA1和SAA2,两者表达水平相当,表达规律相同。检查不同组织SAA1 mRNA表达发现,肝脏是合成SAA1的主要场所,肝外组织也能合成少量SAA1。脓毒症组小鼠外周血出现单体形态的SAA1和SAA2蛋白。

结论

SAA可能具有多种生物学功能,脓毒症外周血血清SAA是SAA1和SAA2的混合物,肝外组织也能够合成一定量的SAA,血清中的单体形态的SAA可以作为脓毒症的生物标志分子。

Objective

To study the biomarkers related to sepsis quantitatively and qualitatively with a CLP mice model and proteomic analysis.

Methods

85 mice were divided into model group and sham operation group to make a model of CLP sepsis in mice, to observe the natural process of the development of sepsis. At the same time, iTRAQ method was used to detect and identify the serum protein at the critical time point. The key molecules closely related to the process of sepsis were determined, and the expression of mRNA in different tissues was observed by qPCR method.

Results

The survival curve showed that 12 - 32 h of sepsis mice was the key time of death, and then went into the natural recovery period. At the same time, a group of proteins were found to match the process in appearance, peak and recovery time. Protein identification confirmed that the proteins included SAA1 and SAA2, and the expression levels were equal. Examination of SAA1 mRNA expression in different tissues revealed that the liver was the main site for the synthesis of SAA1, but extrahepatic tissue was the source of the so-called acute phase response protein SAA1.

Conclusions

SAA may have a variety of biological functions. The serum SAA detected by conventional methods is a mixture of SAA1 and SAA2, and the extrahepatic tissue is the main source of detected serum SAA, which can be used as a biomarker for sepsis. SAA synthesized in the liver is transported through specific pathways and may be involved in the rehabilitation of sepsis.

图1 生存曲线
表1 假手术组与脓毒症组不同时项组间比较(sh,假手术组;se,脓毒症组)
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Apoa5 0.97 0.97 0.99 0.74 0.77 10.4
P值 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
SAA1 0.80 0.62 0.78 0.49 0.64 1.09
P值 >0.05 >0.05 >0.05 >0.05 >0.05 <0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Itih4 1.02 1.27 1.25 0.95 1.38 1.45
P值 >0.05 >0.05 >0.05 >0.05 >0.05 <0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Ang 0.82 0.97 1.91 0.74 1.02 1.38
P值 <0.05 >0.05 >0.05 <0.05 >0.05 <0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Fstl1 1.05 0.88 0.83 1.12 1.15 1.03
P值 >0.05 >0.05 <0.05 >0.05 >0.05 >0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Itih3 0.99 1.13 1.15 0.94 1.17 1.25
P值 >0.05 >0.05 >0.05 >0.05 >0.05 <0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Psmb9 0.96 0.92 0.96 0.81 0.87 1.09
P值 >0.05 >0.05 >0.05 <0.05 >0.05 >0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Lbp 0.93 0.77 0.83 0.69 0.82 1.19
P值 >0.05 <0.05 >0.05 >0.05 >0.05 >0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
SAA2 1.00 0.74 0.74 0.47 0.56 1.18
P值 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Igh-VJ558 1.20 1.05 0.88 1.12 1.35 1.21
P值 >0.05 >0.05 >0.05 >0.05 <0.05 >0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
SAA4 1.20 1.04 0.87 1.01 1.22 1.20
P值 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Pigr 0.96 0.95 0.99 0.82 0.94 1.14
P值 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05
Protein 72 vs 32(sh) 72 vs 8(sh) 32 vs 8(sh) 72 vs 32(se) 72 vs 8(se) 32 vs 8(se)
Masp1 1.20 1.10 1.08 0.87 1.17 1.35
P值 >0.05 >0.05 >0.05 >0.05 <0.05 <0.05
表2 假手术组与脓毒症组相同时项组间比较(sh,假手术组;se,脓毒症组)
图2 CLP小鼠模型血清蛋白聚类热图。(横坐标,重复样本,sh代表假手术组,se代表脓毒症组,第一个"—"后代表时间,第二个"—"代表重复样本;纵坐标为k-mean聚类树状图)
图3 血清蛋白表达相对强度与脓毒症进程的关系
图4 CLP小鼠组织SAA1 mRNA表达
1
Angus DC,Wax RS.Epidemiology of sepsis: An update[J].Crit Care Med,2001,29(7 Suppl):S109-S116.
2
Garcia-Lamberechts EJ,Nunez Orantos MJ,Martin-Sanchez FJ,et al.Epidemiology of sepsis in the emergency care department[J].Med Intensiva,2016,40(5):322.
3
Stoller J,Halpin L,Weis M,et al.Epidemiology of severe sepsis: 2008-2012[J].J Crit Care,2016,31(1):58-62.
4
Zhou J,Tian H,Du X,et al.Population-based epidemiology of sepsis in a subdistrict of beijing[J].Crit Care Med,2017,45(7):1168-1176.
5
He Y,Du WX,Jiang HY,et al.Multiplex cytokine profiling identifies interleukin-27 as a novel biomarker for neonatal early onset sepsis[J].Shock,2017,47(2):140-147.
6
Mikacenic C,Price BL,Harju-Baker S,et al.A two-biomarker model predicts mortality in the critically ill with sepsis[J].Am J Respir Crit Care Med,2017,196(8):1004-1011.
7
梁华平,马晓媛,孙宇.脓毒症的精准诊治-未来的发展方向[J/CD].中华卫生应急电子杂志,2016,2(4):213-216.
8
王正国,梁华平.战创伤感染与脓毒症防治新策略[J/CD].中华卫生应急电子杂志,2015,1(1):1-3.
9
Ahasic AM,Christiani DC.Personalized critical care medicine:How far away are we?[J].Semin Respir Crit Care Med,2015,36(6):809-822.
10
Ludwig KR,Hummon AB.Mass spectrometry for the discovery of biomarkers of sepsis[J].Mol Biosyst,2017,13(4):648-664.
11
Remick DG,Newcomb DE,Bolgos GL,et al.Comparison of the mortality and inflammatory response of two models of sepsis:Lipopolysaccharide vs.Cecal ligation and puncture[J].Shock,2000,13(2):110-116.
12
Wisniewski JR,Zougman A,Nagaraj N,et al.Universal sample preparation method for proteome analysis[J].Nat Methods,2009,6(5):359-362.
13
Chu P,Yan GX,Yang Q,et al.Itraq-based quantitative proteomics analysis of brassica napus leaves reveals pathways associated with chlorophyll deficiency[J].J Proteomics,2015,(113):244-259.
14
Ross PL,Huang YN,Marchese JN,et al.Multiplexed protein quantitation in saccharomyces cerevisiae using amine-reactive isobaric tagging reagents[J].Mol Cell Proteomics,2004,3(12):1154-1169.
15
Sellar GC,Jordan SA,Bickmore WA,et al.The human serum amyloid a protein (saa) superfamily gene cluster: Mapping to chromosome 11p15.1 by physical and genetic linkage analysis[J].Genomics,1994,19(2):221-227.
16
Lowell CA,Potter DA,Stearman RS,et al.Structure of the murine serum amyloid a gene family. Gene conversion[J].J Biol Chem,1986,261(18):8442-8452.
17
De Buck M,Gouwy M,Wang JM,et al.Structure and expression of different serum amyloid a (saa) variants and their concentration-dependent functions during host insults[J].Curr Med Chem,2016,23(17):1725-1755.
18
Ye RD,Sun L.Emerging functions of serum amyloid a in inflammation[J].J Leukoc Biol,2015,98(6):923-929.
19
Getz GS,Reardon CA.SAA,HDL biogenesis,and inflammation[J].J Lipid Res,2008,49(2):269-270.
20
Song C,Hsu K,Yamen E,et al.Serum amyloid a induction of cytokines in monocytes/macrophages and lymphocytes[J].Atherosclerosis,2009,207(2):374-383.
21
De Buck M,Berghmans N,Portner N,et al.Serum amyloid A1α induces paracrine IL-8/CXCL8 via TLR2 and directly synergizes with this chemokine via CXCR2 and formyl peptide receptor 2 to recruit neutrophils[J].J Leukoc Biol,2015,98(6):1049-1060.
22
Gouwy M,De Buck M,Portner N,et al.Serum amyloid a chemoattracts immature dendritic cells and indirectly provokes monocyte chemotaxis by induction of cooperating cc and cxc chemokines[J].Eur J Immunol,2015,45(1):101-112.
23
Connolly M,Marrelli A,Blades M,et al.Acute serum amyloid a induces migration, angiogenesis, and inflammation in synovial cells in vitro and in a human rheumatoid arthritis/scid mouse chimera model[J].J Immunol,2010,184(11):6427-6437.
24
Shah C,Hari-Dass R,Raynes JG.Serum amyloid a is an innate immune opsonin for gram-negative bacteria[J].Blood,2006,108(5):1751-1757.
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