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浙江大学学报（医学版）
浙江大学学报（医学版）  2019, Vol. 48 Issue (6): 587-593    DOI: 10.3785/j.issn.1008-9292.2019.12.01
原著     
缺血性脑损伤大鼠外周血动态共表达网络分析
潘宗富1(),胡晓平1,张轶雯1,李莉2,*(),黄萍1,*()
1. 浙江省人民医院 杭州医学院附属人民医院药学部, 浙江 杭州 310014
2. 浙江省淳安县第一人民医院(浙江省人民医院淳安分院)药剂科, 浙江 杭州 311700
Identification of dynamic co-expression networks in peripheral blood of rats after middle cerebral artery occlusion
PAN Zongfu1(),HU Xiaoping1,ZHANG Yiwen1,LI Li2,*(),HUANG Ping1,*()
1. Department of Pharmacy, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, China
2. Department of Pharmacy, First People's Hospital of Chun'an, Hangzhou 311700, China
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摘要：

目的: 研究大脑中动脉栓塞（MCAO）大鼠不同造模时程外周血的特异表达基因及特征共表达网络模块。方法: 利用GEO数据库的基因表达谱芯片GSE119121联合R语言分析MCAO造模后不同时间点（0、1、2、3、6及24 h）外周血的差异表达基因。通过STEM工具筛选不同造模时程基因表达模式。利用基因本体（GO）数据库和京都基因与基因组百科全书（KEGG）数据库对差异表达的基因进行功能注释和通路富集。在R语言环境下利用CEMiTool包对基因表达谱矩阵进行共表达网络构建及模块分析，并将模块与不同造模时间点进行富集分析。结果: 与造模0 h相比，造模后1、2、3、6及24 h差异表达基因数分别为163、502、527、550、75。共有38种基因表达模式被富集，其中模式65和模式34分别在2~6 h特异上调或下调，Hp、Nos2、P2ry10及Klf12为两种模式的代表性基因。共表达网络模块分析显示，造模急性期早期（1~6 h）基因状态与模块2正相关，造模1~3 h基因状态与模块3正相关，造模2~6 h基因变化与模块4正相关。基因模块6随着造模时间的迁移，与各时间点从正相关（0~2 h）逐渐转为负相关（3~24 h），模块6主要与病毒应答及固有免疫应答相关，其网络核心节点包括Mx1、Mx2、Rtp4等基因。结论: 本研究初步筛选了缺血性脑卒中急性发病期大鼠外周血的特征基因及动态共表达网络模块，为探究缺血性脑卒中的病理生理变化规律提供了依据。
关键词： 缺氧缺血, 脑/血液;  卒中/血液;  基因表达;  基因调控网络    
Abstract:

Objective: To identify the time dependent profiles of gene expression and featured co-expression network modules in peripheral blood of rats after middle cerebral artery occlusion (MCAO). Methods: Microarray GSE119121 from GEO database was analyzed by R language to identify the significantly changed genes in peripheral blood at different time points (0, 1, 2, 3, 6 and 24 h) after MCAO. Gene expression patterns at different time courses were screened by STEM tools. Then, function annotation and pathway enrichment of differentially expressed genes (DEGs) were performed using the Gene Ontology (GO) database and the Kyoto Gene and Genomic Encyclopedia (KEGG) database. Depending on CEMiTool package, gene expression profile matrix was inputted into R to construct the co-expression networks and to analyze modules, and enrichment analysis was conducted to evaluate the correlation between the modules and different time points. Results: Comparing with gene at 0 h, the numbers of DEGs in peripheral blood at different time points after MCAO were 163 (1 h), 502 (2 h), 527 (3 h), 550 (6 h), and 75 (24 h), respectively. Moreover, a total of 38 gene expression patterns were enriched, and pattern 65 and pattern 34 were specifically up-regulated or down-regulated at 2-6 h. Hp, Nos2, P2ry10, and Klf12 were representative genes of these two models. The co-expression network module analysis showed that the gene status in the early acute phase (1-6 h) was positively correlated with the Module 2. Module 3 and Module 4 was positively correlated with phase phase 1-3 h and 2-6 h, respectively. Noteworthy, Module 6 gradually changed from positive correlation (0-2 h) to negative correlation (3-24 h) with the MCAO time course, and Module 6 was mainly related to viral response and innate immune response. The hub genes of Module 6 included Mx1, Mx2, and Rtp4. Conclusion: Our study has identified the featured genes and dynamic co-expression network modules in peripheral blood after acute ischemic stroke, which provides a potential basis for judging the onset time of ischemic stroke.
Key words: Hypoxia-ischemia, brain/blood    Stroke/blood    Gene expression    Gene regulatory networks
收稿日期: 2019-06-08 出版日期: 2020-01-19
CLC:  R743.3  
基金资助: 国家自然科学基金(81802673);浙江省公益性技术研究计划(LQ18H160017);浙江省医药卫生科技计划(2017KY023);杭州市卫生科技计划(2017B56)
通讯作者: 李莉,黄萍     E-mail: panzongfu@163.com;420683321@qq.com;huangping1841@zjcc.org.cn
作者简介: 潘宗富(1989—), 男, 博士, 主管药师, 主要从事神经再生研究; E-mail:panzongfu@163.com; https://orcid.org/0000-0002-4054-6660
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引用本文:

潘宗富,胡晓平,张轶雯,李莉,黄萍. 缺血性脑损伤大鼠外周血动态共表达网络分析[J]. 浙江大学学报（医学版）, 2019, 48(6): 587-593.

PAN Zongfu,HU Xiaoping,ZHANG Yiwen,LI Li,HUANG Ping. Identification of dynamic co-expression networks in peripheral blood of rats after middle cerebral artery occlusion. J Zhejiang Univ (Med Sci), 2019, 48(6): 587-593.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.12.01    或    http://www.zjujournals.com/med/CN/Y2019/V48/I6/587

上调基因 Log差异倍数 校正后的P值
Fpr1 2.37 1.74×10-9
Il1r2 2.29 3.88×10-12
Mrgprx3 2.16 3.39×10-12
Mmp9 2.06 1.85×10-9
Ifitm6 1.89 4.06×10-8
Olfm4 1.78 2.24×10-7
Amica1 1.75 2.50×10-8
Bmx 1.69 4.32×10-9
Mir223 1.68 1.37×10-7
Ldhc 1.64 4.71×10-10
LOC679818 1.63 1.98×10-8
Fkbp5 1.62 1.87×10-11
Pram1 1.55 9.02×10-10
Hp 1.52 4.51×10-8
Stfa3 1.51 0.000505
Cd33 1.51 8.86×10-9
Cd177 1.50 1.47×10-6
Alox5 1.50 8.04×10-9
Ugt8 1.49 5.65×10-9
Dhrs9 1.49 1.78×10-9
Clec5a 1.46 1.21×10-6
Mmp25 1.45 1.24×10-8
Nlrp12 1.44 1.87×10-9
Mcemp1 1.44 1.39×10-9
Camp 1.44 2.04×10-8
LOC24906 1.43 4.82×10-10
Mir292 1.43 4.95×10-7
Dgat2 1.41 1.43×10-8
Il18rap 1.40 2.64×10-9
Cpm 1.39 3.11×10-7
Oas1k 1.38 1.32×10-8
Pglyrp4 1.38 4.83×10-9
Adgrg3 1.37 1.48×10-10
Tnnc1 1.36 1.49×10-6
Fcar 1.36 1.08×10-9
P2ry13 1.36 1.08×10-9
Tcn2 1.34 2.85×10-10
Rab44 1.34 1.51×10-10
Nos2 1.33 8.04×10-9
LOC690020 1.33 4.47×10-6
Hk3 1.33 9.13×10-11
LOC102557597 1.32 2.23×10-6
Lcn2 1.32 7.49×10-5
Aqp9 1.30 1.41×10-7
Rgs1 1.28 0.001199
Rbm47 1.26 3.45×10-8
Tarm1 1.25 1.10×10-5
Alox5ap 1.24 1.71×10-9
LOC689230 1.22 5.29×10-5
Uaca 1.22 3.15×10-8
附表 1  大脑中动脉栓塞模型大鼠造模后1 h外周血上调倍数前50位基因
下调基因 Log差异倍数 校正后的P值
Cd79b -1.91 3.47×10-10
Fcmr -1.79 3.88×10-12
Ebf1 -1.79 1.59×10-9
LOC501110 -1.76 2.55×10-8
Fcer2 -1.74 1.06×10-9
B3gnt5 -1.72 2.93×10-9
Fcrla -1.70 1.48×10-10
Hvcn1 -1.67 2.85×10-10
Igd -1.64 1.72×10-10
Ms4a1 -1.61 3.76×10-9
RT1-Da -1.60 4.82×10-10
Pde6h -1.53 1.80×10-7
Cd79al -1.53 4.82×10-10
Swap70 -1.53 7.49×10-12
Cd19 -1.48 1.31×10-10
Bank1 -1.48 3.88×10-12
Rnase6 -1.47 8.79×10-7
Cd180 -1.46 5.10×10-8
Bcl11a -1.40 1.13×10-7
Btla -1.40 3.47×10-10
Nrp1 -1.40 1.69×10-10
Cd209a -1.38 1.08×10-9
Cd74 -1.38 3.76×10-9
Myo1e -1.36 1.87×10-11
Blnk -1.31 1.08×10-9
Eno3 -1.31 9.02×10-10
Kynu -1.27 1.87×10-7
RGD1560455 -1.27 7.87×10-7
Acsl3 -1.26 9.07×10-8
Rnase4 -1.26 3.52×10-7
Gngt2 -1.25 1.71×10-9
LOC100361706 -1.25 1.21×10-9
Qrfpr -1.23 3.56×10-7
LOC100911716 -1.20 2.02×10-8
Ly86 -1.19 1.37×10-7
Samhd1 -1.18 1.52×10-8
Zfp958 -1.17 1.29×10-6
Trpm6 -1.16 4.68×10-8
Mal -1.15 1.82×10-8
Fchsd2 -1.13 1.85×10-9
Ell3 -1.13 3.88×10-8
Akap17b -1.13 1.59×10-9
Crip1 -1.12 1.91×10-6
Cd22 -1.12 2.20×10-7
Ifi30 -1.09 3.40×10-8
Insig1 -1.09 2.29×10-7
Snrpd1 -1.09 0.000153
Cd200 -1.09 2.65×10-9
Plxnb2 -1.07 2.80×10-8
Klf4 -1.07 2.50×10-8
附表 2  大脑中动脉栓塞模型大鼠造模后1 h外周血下调倍数前50位基因
上调基因 Log差异倍数 校正后的P值
Il1r2 2.96 1.45×10-14
Ifitm6 2.86 1.10×10-10
Mrgprx3 2.83 4.47×10-14
Fpr1 2.81 1.23×10-11
Mmp9 2.75 6.37×10-12
Hp 2.61 1.49×10-12
Pram1 2.48 7.24×10-14
Olfm4 2.48 7.55×10-10
Mmp25 2.48 2.57×10-12
Cd33 2.47 1.84×10-12
Bmx 2.45 3.97×10-12
Cpm 2.27 4.15×10-11
Nos2 2.26 2.63×10-12
Mir292 2.22 3.04×10-10
Stfa3 2.17 6.88×10-8
Dgat2 2.17 7.12×10-13
LOC679818 2.17 8.00×10-12
Mcemp1 2.16 7.24×10-14
Alox5 2.14 6.00×10-12
Oas1k 2.14 1.37×10-11
Camp 2.13 9.61×10-11
Ldhc 2.13 6.86×10-13
Rab44 2.12 3.24×10-14
Dhrs9 2.11 2.57×10-12
Ppp1r3b 2.10 3.95×10-13
Adgrg6 2.10 1.84×10-12
Amica1 2.09 9.94×10-11
Tas2r126 2.08 2.32×10-9
Tnnc1 2.07 2.57×10-10
Rbm47 2.07 7.65×10-13
Ugt8 2.07 2.49×10-11
Uaca 2.06 3.38×10-12
Hk3 2.06 4.64×10-13
LOC690020 2.04 7.29×10-8
Prok2 2.02 2.39×10-11
LOC689230 2.01 2.92×10-8
Tcn2 2.00 4.59×10-14
Nlrp12 2.00 2.57×10-12
LOC24906 2.00 1.84×10-12
Fkbp5 1.99 3.95×10-13
Slc2a3 1.98 6.82×10-12
LOC102557597 1.95 9.34×10-11
Alox5ap 1.92 1.98×10-13
Tarm1 1.92 2.10×10-9
Stfa2l2 1.91 3.96×10-11
Clec5a 1.91 2.64×10-9
Il18rap 1.90 2.97×10-11
Amdhd1 1.90 1.37×10-11
Cd177 1.89 2.66×10-8
Bcr 1.88 1.16×10-13
附表 3  大脑中动脉栓塞模型大鼠造模后2 h外周血上调倍数前50位基因
下调基因 Log差异倍数 校正后的P值
Ms4a1 -2.54 3.24×10-14
Ebf1 -2.36 4.39×10-13
Cd79b -2.33 1.39×10-12
B3gnt5 -2.30 1.39×10-12
Hvcn1 -2.24 4.59×10-14
Fcer2 -2.22 3.74×10-14
RGD1560455 -2.20 8.21×10-11
Fcmr -2.18 3.74×10-14
LOC501110 -2.16 2.57×10-10
Igd -2.16 4.59×10-14
Fcrla -2.11 4.59×10-14
Btla -2.06 5.44×10-13
Cd19 -2.01 5.06×10-14
Rnase6 -2.00 8.35×10-12
Cd79al -1.97 2.97×10-13
Nrp1 -1.96 3.24×10-14
Cd180 -1.96 3.80×10-11
Bcl11a -1.88 2.39×10-11
Bank1 -1.87 3.74×10-14
Pde6h -1.86 2.37×10-9
RT1-Da -1.82 2.83×10-12
Eno3 -1.80 3.69×10-12
Fcrl1 -1.76 2.69×10-10
Trpm6 -1.73 1.93×10-12
Blnk -1.72 2.96×10-13
Kynu -1.67 6.65×10-10
Qrfpr -1.67 1.26×10-9
P2ry10 -1.65 2.68×10-11
Insig1 -1.63 1.50×10-10
LOC100361706 -1.62 1.30×10-11
Gpr174 -1.58 2.47×10-11
Cd209a -1.57 1.56×10-11
Immp1l -1.57 5.86×10-8
Cd74 -1.56 2.41×10-11
Ell3 -1.54 1.63×10-10
Ly86 -1.54 7.50×10-10
Slc25a36 -1.52 3.87×10-8
Cmah -1.51 4.39×10-13
Gngt2 -1.50 2.48×10-10
Lax1 -1.49 8.93×10-11
Swap70 -1.49 1.08×10-13
Myo1e -1.48 6.18×10-13
Cd22 -1.48 1.99×10-11
Rhoh -1.48 1.35×10-11
LOC100911716 -1.47 6.71×10-9
Slc9a7 -1.47 1.64×10-10
Fam49a -1.44 4.35×10-11
LOC499229 -1.44 1.60×10-10
Mal -1.43 1.13×10-10
Ccdc50 -1.42 4.23×10-12
附表 4  大脑中动脉栓塞模型大鼠造模后2 h外周血下调倍数前50位基因
上调基因 Log差异倍数 校正后的P值
Hp 3.22 6.28×10-14
Plscr1 3.14 6.49×10-13
Tgm1 3.05 2.66×10-12
Il1r2 3.03 1.74×10-15
Ifitm6 2.94 1.14×10-11
Cd33 2.81 1.56×10-13
Serpinb1a 2.68 1.56×10-13
Nos2 2.66 4.80×10-15
Fpr1 2.57 2.26×10-11
Ugt8 2.56 2.99×10-11
Prok2 2.54 1.07×10-13
Dgat2 2.49 2.63×10-13
Bmx 2.46 1.95×10-12
Mmp25 2.45 2.15×10-13
Dhrs9 2.44 6.86×10-13
Olfm4 2.40 2.06×10-9
Pram1 2.40 2.94×10-13
Cpne8 2.39 1.81×10-11
Dab2 2.33 1.51×10-10
Mmp9 2.33 1.74×10-11
Vcan 2.32 2.27×10-11
Ppp1r3b 2.32 3.68×10-13
Cpm 2.31 1.14×10-11
Mrgprx3 2.22 3.37×10-14
Rab44 2.21 3.66×10-15
Tarm1 2.20 1.80×10-10
P2ry13 2.13 1.29×10-12
Ampd3 2.13 5.53×10-12
Csf2rb 2.12 3.54×10-14
Rrm2 2.12 2.23×10-12
Slc2a3 2.12 8.29×10-12
Rbm47 2.11 1.70×10-10
Oas1k 2.09 1.63×10-12
Mcemp1 2.07 5.12×10-13
Crispld2 2.07 2.73×10-13
Adgrg6 2.06 2.15×10-13
Msr1 2.05 2.36×10-11
Tfec 2.04 1.82×10-8
Slpi 2.03 5.15×10-13
Nlrp12 2.01 3.38×10-12
Slc5a3 2.01 1.51×10-10
Il18rap 1.99 4.99×10-12
LOC679818 1.99 6.06×10-11
Il1rap 1.98 1.87×10-11
Hk2 1.98 3.71×10-12
Tpd52 1.95 1.56×10-13
Gk 1.94 1.04×10-9
Upp1 1.93 1.95×10-12
Mocos 1.92 1.74×10-11
Hk3 1.92 1.51×10-13
附表 5  大脑中动脉栓塞模型大鼠造模后3 h外周血上调倍数前50位基因
下调基因 Log差异倍数 校正后的P值
Rnase6 -2.56 3.38×10-12
Ms4a1 -2.48 7.64×10-14
Ebf1 -2.42 5.15×10-13
Cd79b -2.35 1.04×10-12
Fcer2 -2.24 3.60×10-13
Fcrla -2.21 7.54×10-14
LOC501110 -2.21 2.40×10-8
Fcmr -2.18 1.74×10-15
Nrp1 -2.18 1.42×10-14
Cd79al -2.15 1.67×10-13
Cd180 -2.14 8.93×10-11
Igd -2.14 1.67×10-13
Btla -2.13 9.53×10-13
Hvcn1 -2.10 2.71×10-12
Eno3 -2.06 1.66×10-14
B3gnt5 -2.03 6.49×10-13
Cd19 -2.00 1.64×10-12
RGD1560455 -1.98 4.79×10-8
Bank1 -1.91 3.40×10-15
Gngt2 -1.87 1.64×10-12
Pde6h -1.87 2.84×10-10
Ly86 -1.83 8.27×10-10
P2ry10 -1.80 3.61×10-10
LOC100361706 -1.79 3.32×10-13
Dnase2b -1.76 6.94×10-10
Trpm6 -1.73 4.59×10-11
Heg1 -1.72 1.67×10-13
Gpr174 -1.71 4.81×10-10
Blnk -1.65 6.49×10-13
Cd209a -1.65 1.30×10-11
Il5ra -1.64 8.27×10-12
Hmgn3 -1.64 1.43×10-10
Cd22 -1.63 1.22×10-11
Xkrx -1.62 5.78×10-9
Cmah -1.60 3.38×10-12
Nr4a1 -1.60 1.91×10-10
Qrfpr -1.59 3.55×10-9
Slc6a12 -1.58 6.40×10-12
Mal -1.58 7.79×10-11
Ccdc50 -1.55 2.15×10-12
Fam49a -1.55 8.21×10-10
Spn -1.54 1.56×10-12
Lax1 -1.52 6.04×10-11
Klf12 -1.52 5.20×10-12
Adgre1 -1.52 2.08×10-9
Fcrl1 -1.51 5.40×10-11
Cd24 -1.50 1.90×10-10
Bcl11a -1.50 2.28×10-10
Trat1 -1.49 1.23×10-8
Ell3 -1.48 8.40×10-12
附表 6  大脑中动脉栓塞模型大鼠造模后3 h外周血下调倍数前50位基因
上调基因 Log差异倍数 校正后的P值
Tgm1 4.06 1.99×10-12
Cpne8 3.76 6.80×10-15
Ifitm6 3.61 7.01×10-12
Hp 3.57 1.72×10-13
Serpinb1a 3.50 6.80×10-15
Olfm4 3.31 4.23×10-10
Il1r2 3.31 8.33×10-15
Prok2 3.17 1.01×10-13
Clec4b2 3.16 5.43×10-13
Adgb 3.10 1.31×10-11
Cd33 3.07 4.97×10-13
Plscr1 2.97 3.36×10-13
Wfdc15b 2.84 6.80×10-15
Mmp25 2.83 1.31×10-11
Ugt8 2.83 4.91×10-12
Lcn2 2.79 7.32×10-8
Il1rap 2.77 7.32×10-13
Slpi 2.75 1.01×10-13
Rrm2 2.72 3.11×10-13
Bmx 2.70 2.49×10-12
Dgat2 2.67 3.41×10-12
Car4 2.67 2.43×10-10
Sycp2 2.63 4.57×10-12
Gk 2.62 7.97×10-12
Tas2r126 2.62 1.79×10-10
Msr1 2.61 1.12×10-11
Tarm1 2.59 1.06×10-10
Nos2 2.58 3.41×10-12
Fpr1 2.57 1.97×10-10
Oscar 2.55 6.72×10-12
Slc2a3 2.55 3.23×10-12
Il22ra2 2.54 1.43×10-12
Slc5a3 2.49 4.01×10-13
Ampd3 2.48 1.55×10-11
Mmp9 2.43 2.43×10-10
LOC102557597 2.42 2.62×10-10
Vcan 2.42 1.92×10-11
Pram1 2.40 2.43×10-12
Ccr1 2.40 8.43×10-12
Tas2r143 2.36 5.07×10-12
Nlrp12 2.35 5.07×10-12
Crispld2 2.35 4.16×10-12
Tas2r135 2.34 2.51×10-9
Gca 2.31 7.33×10-10
Cpm 2.31 8.47×10-11
Alox5ap 2.31 2.73×10-13
P2ry13 2.29 8.30×10-13
Csf2rb 2.26 3.69×10-12
RGD1307182 2.26 1.72×10-11
Alpk1 2.25 5.49×10-11
附表 7  大脑中动脉栓塞模型大鼠造模后6 h外周血上调倍数前50位基因
下调基因 Log差异倍数 校正后的P值
Rnase6 -2.58 7.17×10-11
Eno3 -2.23 1.38×10-13
Mx2 -2.16 6.58×10-14
Fcer2 -2.07 6.49×10-12
Ebf1 -1.95 1.77×10-11
Ms4a1 -1.94 4.04×10-11
Cd79al -1.93 7.32×10-13
Adgre1 -1.93 3.78×10-10
Dnase2b -1.92 6.01×10-10
Fcrla -1.91 2.30×10-12
Cd79b -1.89 1.16×10-10
Fcmr -1.88 5.16×10-13
Slc6a12 -1.82 1.10×10-12
Hvcn1 -1.78 8.00×10-12
Il5ra -1.72 6.34×10-10
Nrp1 -1.72 3.56×10-11
Mx1 -1.71 1.10×10-12
P2ry10 -1.69 9.78×10-9
LOC100361706 -1.66 1.31×10-11
Cd19 -1.66 1.05×10-11
Btla -1.62 1.49×10-9
Emr4 -1.59 2.32×10-8
LOC103692555 -1.59 9.79×10-5
Ly86 -1.58 1.77×10-9
Cd180 -1.58 8.22×10-10
Cd4 -1.58 3.41×10-12
Igd -1.57 3.58×10-10
MGC108823 -1.55 9.90×10-8
Gpr174 -1.54 2.76×10-8
Cd24 -1.53 6.19×10-10
LOC501110 -1.53 1.09×10-7
Bank1 -1.52 1.58×10-11
Bcl2 -1.52 9.74×10-12
Camk2d -1.50 1.00×10-10
Ddx60 -1.49 1.18×10-8
Blnk -1.48 6.79×10-11
B3gnt5 -1.48 5.04×10-9
Myo1e -1.47 2.36×10-11
Cxcl16 -1.47 1.73×10-9
Heg1 -1.47 9.74×10-12
Trpm6 -1.47 1.32×10-9
Nr4a1 -1.46 4.71×10-10
Lbh -1.45 8.22×10-10
Gngt2 -1.45 4.08×10-11
Gapt -1.45 1.39×10-8
RGD1309362 -1.44 7.49×10-9
Cd28 -1.44 1.26×10-8
Mras -1.44 1.92×10-11
Ms4a6c -1.43 5.39×10-8
Atp2b4 -1.43 4.11×10-11
附表 8  大脑中动脉栓塞模型大鼠造模后6 h外周血下调倍数前50位基因
上调基因 Log差异倍数 校正后的P值
Fetub 1.96 3.27×10-6
Cd33 1.87 3.31×10-7
Cpne8 1.80 1.06×10-5
Clec4b2 1.64 1.81×10-5
Tas2r126 1.55 6.15×10-6
Prok2 1.52 6.54×10-6
LOC679818 1.49 4.84×10-6
Serpinb1a 1.47 0.000168
Tarm1 1.47 6.78×10-6
Oscar 1.42 9.67×10-6
Prg4 1.40 0.000124
Adgb 1.37 0.000141
Bmx 1.35 1.14×10-5
Nlrp12 1.32 4.02×10-6
Serpinb2 1.31 1.08×10-5
Wfdc15b 1.30 1.20×10-7
Nek10 1.30 0.000397
Car4 1.26 8.91×10-5
Il22ra2 1.26 1.29×10-5
Ugt8 1.24 3.36×10-5
Slc12a2 1.23 4.73×10-7
Slpi 1.23 2.27×10-5
Il1r2 1.23 0.00013
Tfrc 1.22 8.13×10-7
Mir223 1.21 6.63×10-5
Ampd3 1.18 6.42×10-5
Slc7a11 1.17 5.61×10-6
Slc2a3 1.17 8.30×10-5
Mir292 1.16 2.30×10-5
Tspan8 1.16 1.99×10-5
Dgat2 1.14 0.000201
Mmp25 1.14 7.08×10-5
Mcemp1 1.14 0.000123
Tas2r143 1.13 1.59×10-5
Fpr1 1.13 0.000638
Il1rap 1.12 6.03×10-5
Bco1 1.11 2.07×10-7
Siglec8 1.10 2.60×10-5
Vcan 1.07 5.38×10-5
Gk 1.06 0.000146
Ccr1 1.05 0.000726
Ifitm6 1.05 0.014119
Fbxl5 1.03 1.32×10-5
Sort1 1.02 6.98×10-7
Fam92a1 1.01 2.22×10-7
Tns1 1.01 2.10×10-5
Bst1 1.01 2.93×10-5
Mir290 1.01 2.27×10-5
附表 9  大脑中动脉栓塞模型大鼠造模后24 h外周血上调基因
下调基因 Log差异倍数 校正后的P值
Mx2 -2.15 2.53×10-11
Rnase6 -1.84 1.87×10-7
Rtp4 -1.76 2.49×10-9
Mx1 -1.59 2.49×10-9
Igj -1.50 1.23×10-7
MGC108823 -1.34 1.38×10-6
LOC102556096 -1.29 2.92×10-6
Eno3 -1.26 3.02×10-7
Oas1b -1.21 7.97×10-7
LOC689230 -1.21 0.000732
Irgm -1.17 1.87×10-7
Ddx60 -1.14 3.27×10-6
Nrp1 -1.13 3.21×10-7
Ly6e -1.10 4.76×10-7
Slc6a12 -1.10 2.07×10-7
LOC100362391 -1.07 2.77×10-6
Spn -1.07 1.87×10-7
Slamf9 -1.07 4.73×10-7
Snrpd1 -1.04 0.00011
RGD1309362 -1.03 3.31×10-7
Epsti1 -1.02 1.20×10-7
Mras -1.02 8.15×10-8
Trat1 -1.02 3.52×10-6
Snrpf -1.01 3.87×10-5
Ngp -1.00 0.003918
Oas2 -1.00 8.13×10-7
附表 10  大脑中动脉栓塞模型大鼠造模后24 h外周血下调基因
附图1  大脑中动脉栓塞模型大鼠造模后外周血差异表达基因及特征基因
附图2  MCAO造模后不同时间点外周血差异基因的基因本体（生物进程）注释
附图3  MCAO造模后不同时间点外周血差异基因的KEGG通路富集
附图4  MCAO造模不同时间点外周血特征共表达模块分析
附图5  共表达模块蛋白互作用网络构建及核心基因分析
附图6  共表达模块基因本体注释及KEGG通路富集
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