Bioinformatic analysis of differentially expressed genes in muscle atrophy tissues after spinal cord injury
-
摘要:目的 通过生物信息学方法分析脊髓损伤后肌肉萎缩患者肌肉组织的差异表达基因,筛选出与该病相关基因。方法 选取基因表达数据库(GEO)中GSE21497芯片,通过R语言软件筛选出差异基因。将筛选出的差异表达基因进行GO、KEGG分析,构建蛋白质互作用网络。使用分子复合物检测算法(MCODE)筛选相互作用紧密的显著差异表达基因。结果 筛选得出294个差异表达基因,其中8个上调表达基因,286个下调表达基因。GO富集分析中,差异基因主要存在于肌质、肌膜、肌球蛋白复合物等结构,主要涉及肌肉构成和β-连环蛋白、热休克蛋白等物质的结合,主要参与肌肉系统发育、调控细胞分化与凋亡、突触修剪等过程。通过蛋白质互相作用网络(PPI Network)筛选出18个可能与脊髓损伤后肌肉萎缩发生发展紧密相关的差异表达基因,包括TNNI1、GYS1、C1QA等。结论 本研究筛选出的差异表达基因可为深入探索脊髓损伤后肌肉萎缩的机制及治疗提供新的思路。Abstract:Objective To analyze the differentially expressed genes in muscular tissue of patients with muscle atrophy after spinal cord injury by bioinformatic analysis, and the genes related to the disease were screened out.Methods The GSE21497 chip from Gene Expression Omnibus (GEO) was selected and the differential genes were screened by R language software. The screened differentially expressed genes were analyzed by GO and KEGG, and the protein interaction network was constructed. Molecular Complex Detection Algorithm (MCODE) was used to screen for significantly differentially expressed genes with close interactions.Results A total of 294 differentially expressed genes were screened, including 8 up-regulated genes and 286 down-regulated genes. In GO enrichment analysis, differential genes mainly existed in the structure of myosin complex, myosin complex and myosin complex, involved the binding of muscle composition and combination of β-catenin, heat shock protein and other substances, and mainly involved in muscle phylogeny, regulation of cell differentiation and apoptosis, synaptic pruning and other processes. Totally 18 differentially expressed genes that might be closely related to the occurrence and development of muscle atrophy after spinal cord injury were screened through the Protein Protein Interaction Network (PPI Network), including TNNI1, GYS1, C1QA and so on.Conclusion The differentially expressed genes screened in this study can provide a new way to further explore the mechanism and treatment of muscle atrophy after spinal cord injury.
-
脊髓损伤是神经外科一类重症疾病,可分为创伤性和非创伤性脊髓损伤,前者较为常见,常由外部物理因素引起[1], 后者常由肿瘤、缺血或先天性疾病引起[2]。脊髓损伤通过神经元损害、肌肉废用等途径引起骨骼肌萎缩[3-4]。目前已有学者对脊髓组织损伤后继发的线粒体功能障碍、氧化应激激活、肌肉蛋白质合成与降解等过程进行了相关研究[5-6], 但其病理、生理的复杂性限制了该病的治疗进展。本研究对脊髓损伤后肌肉萎缩患者的肌肉组织进行生物信息学分析,并探讨该病的发病机制,以期为潜在治疗方法提供理论依据,现报告如下。
1. 资料与方法
1.1 基因芯片的筛选
选择GEO数据库中GPL570[HG-U133_Plus_2]Affymetrix Human Genome U133 Plus 2.0 Array平台检测,编号为GSE21497的芯片进行分析。此芯片从招募的10位脊髓损伤肌肉萎缩的患者中获取骨骼肌样本,其中包括脊髓损伤患者男9例和女1例(6例为四肢瘫痪, 4例为截瘫),平均年龄44岁。入选标准: 18岁以上患者; 格拉斯哥昏迷评分大于13分者; 无肌肉挤压伤、低氧损伤、系统性败血症、全身性炎症者; 自身免疫性疾病及恶性肿瘤者。分别在脊髓损伤后第2、5天使用5mm Berstrom活检针从10位患者的股外侧肌获取肌肉样本,取下后立即置入液氮中冻存,储存于-80℃待测。以患者第2天的股外侧肌样本的基因表达谱数据为对照组,以第5天样本的基因表达谱数据作为实验组。
1.2 芯片数据处理与差异基因提取
使用R软件中affyPLM、RColorBrewer包进行芯片数据分析,得出相对对数表达图,观察各组样本数据表达强度。然后调用R软件中affyPLM、affy包通过RMA算法对芯片进行背景校正。利用R软件中limma包,设置差异基因筛选条件: logFC>1或logFC < (-1), 且adj. P. val < 0.05。将提取的差异基因导入OmicShare(https://www.omicshare.com/)在线网站制作出火山图、热图。
1.3 差异基因富集分析
将筛选出的差异基因导入Metascape在线网站,进行GO分析、KEGG信号通路分析,以柱状图表现富集结果,获取基因相关的生物学过程(BP)、细胞组分(CC)、分子功能(MF)。
1.4 构建蛋白质互作用网络
将筛选出的差异基因导入Metascape在线网站,进行蛋白互作网络构建。利用MCODE算法检测出相互作用结果紧密的蛋白质模块中的关键差异基因。
2. 结果
2.1 脊髓损伤后肌肉萎缩患者肌肉组织中的差异基因
使用R软件得出相对对数表达图,每个样品的中心均较接近纵坐标0, 结果表明样本平行试验一致性较强,见图 1A。样本背景校正后,设置差异倍数大于2及校正后P值小于0.05, 筛选出294个差异基因。2组样本中共有8个上调表达差异基因, 286个下调表达差异基因,见表 1。将差异基因导入OmicShare在线网站制作热图和火山图,见图 1B、图 1C。
表 1 脊髓损伤肌肉萎缩患者第2、5天肌肉样本的差异基因上调(8个基因) LOC646903、GADD45A、PRRT3-AS1、MSTN、MAP3K7CL、RCSD1、E2F8、LSMEM1 下调(286个基因) TNFRSF18、PRB4、CA9、SEMA5B、GCK、KLRG1、LINC00868、KIAA0040、C16orf71、FAM223B、LOC283194、CSF3、LILRB1、LOC101928111、CA14、LOC101929897、LGALS9、SHISA3、CCDC64B、RTCA、C11orf84、RASSF4、ASPRV1、PORCN、ANKRD34A、MEDAG、LOC101060424、TGM7、BEX4、ST3GAL1、KIF3B、PEX11A、PPARGC1A、F3、XAGE-4、FOXP1-IT1、PARG、HOXC11、CLEC2L、RETSAT、TNFSF13、MYL3、PROCR、ANKRD2、TP53INP2、NEDD4L、NID1、MFAP5、PRKCD、DAXX、FCN3、MYH7、MAP1B、HSD17B11、BBS10、PTPRU、ANGPTL7、SLC27A4、AOX1、FHL5、FABP7、METTL7A、KDR、FAM110D、NDUFC1、RC3H1、KCNB1、SMAP2、CDC37L1、RNF25、NMNAT1、SMAD3、ARID5B、CHN2、SSPN、WBP1L、CYP4B1、CPAMD8、ASAH1、LMCD1、UGP2、ZNF438、C1orf162、PSD、TFPT、ACSM5、COL6A3、RPN1、FAM166B、PDE7A、PIK3CB、DIO2、TSPYL2、SGMS1、MLXIPL、LIX1L、SLC7A2、NMRK2、NCOA3、FEM1C、SMS、MOCOS、VLDLR、FOXO3、LIFR、DDIT4、GPT2、HOMER1、GPX7、MTFP1、EPHB1、TMEM45A、CHAC1、ALOX5AP、SLC19A2、GOT1、PTPRG、SORT1、ITGAM、RASSF1、SLC16A9、LAMB1、P2RY14、MYOM2、PLIN3、ANG、AKR1B10、PRCC、ZBTB16、PIBF1、PKD2、MFGE8、ELF1、LZTS3、HCLS1、THBS2、SLC38A2、METRNL、ECI2、ACSL1、ACTN2、ZNF385B、HSF2、LINC00312、FIBIN、SPSB1、PDK4、SAMD13、CA3、ITGB1BP2、PRKAG3、MT1M、SIRT1、SRPX、NPTX2、ENKD1、C1orf198、LTBP2、YAP1、GPCPD1、FKBP5、FSD2、CPM、CLIC4、FLJ36848、KIAA1161、CNST、ANKRD27、LPIN1、MYOM3、DNAJA4、BLM、MMP3、SLC25A1、RAB23、PRELP、CASQ2、IL1R2、PANK1、PIK3R1、COL5A2、INHBB、ITGA10、ADAMTS5、COL4A1、VIT、RNASE4、CLIC6、ACACB、EBF1、APCDD1、COQ10A、DNAJB5、TSPAN5、BZW1、MYLK4、FBN1、RND3、FOSL2、FAM65B、ROBO1、ANO5、ENPP5、DHRS7C、AGTR1、DHCR24、ANKMY2、GLUL、S100A9、PCYOX1、CD163、IGFBP6、WIPI1、FABP3、RBP4、NFIL3、LINC00948、FAM46C、MIOS、SLC38A1、C5orf27、TNKS1BP1、CNN3、CSPP1、PLAT、C20orf166、SOD2、TMEM208、VCL、SLC2A4、ARHGEF3、GADD45G、LYVE1、SAMHD1、SMAD7、MYL2、GALNT15、SIMC1、SNAI2、FOXO1、HSPA2、SH2D1B、C1QC、TIMP4、VSIG4、MRC1、GGT7、ARG2、RASSF5、SMAD9、IRX3、C1QA、CALML6、SERPINA5、MIR646HG、MYH2、LOC101927391、ABRA、OLFML2A、KLF5、LINC01405、DAAM2、TCAP、IGFBP3、MGST1、RASD1、LINC00844、MAOA、CIDEC、F13A1、GYS1、SLC25A33、C1QB、FBP2、MYOZ2、MAFB、C12orf75、LRRN3、LOC643659、PLTP、CTGF、ECHDC3、FAM179A、PEBP4、TNNC1、TNNI1 2.2 差异基因的GO、KEGG分析
GO富集中, CC中差异基因主要集中于肌纤维组分、肌质、异构SMAD蛋白复合体、肌球蛋白复合物、肌膜、细胞器外膜。分子MF中差异基因主要集中于肌肉的结构组分、肌动蛋白结合、生长因子结合、整联蛋白结合、碳水化合物结合、β-连环蛋白结合、热休克蛋白结合、碳酸脱水酶活性、脂肪酸连接酶活性、阴离子跨膜转运蛋白活性。BP中差异基因主要集中于肌肉器官发育过程、细胞衰亡的正向调控、细胞增殖、分化的负向调控、能量平衡、脂肪细胞分化、细胞对外部刺激的反应、对氮化合物的反应、对酸性化学物质的反应、活性氧代谢过程、辅因子生物合成、突触修剪等。见图 2。
KEGG信号通路主要包括: 补体系统信号通路、FoxO信号通路、黏着斑信号通路、氮素代谢信号通路、精氨酸和脯氨酸代谢信号通路、过氧化物酶体增殖物激活受体信号通路、谷胱甘肽代谢信号通路、铁死亡信号代谢通路、烟酸和烟酰胺代谢信号通路、半乳糖代谢信号通路等。
2.3 蛋白质相互作用分析及关键差异基因获取
蛋白质互作用网络中, 4个蛋白相互作用较丰富模块中的关键基因共有18个: TNNI1、TNNC1、TCAP、ACTN2、MYL3、MYL2、DNAJA4、DNAJB5、GYS1、UGP2、AKR1B10、GOT1、C1QA、C1QB、C1QC、CASQ2、DAXX、SLC2A4, 见图 3。
3. 讨论
脊髓损伤导致肌肉萎缩,亦使全身多系统继发严重功能障碍[6]。研究[7-8]表明,在脊髓损伤后6周内,骨骼肌平均横截面积比对照组低18%~46%, 且身体总脂肪率增高。肌肉萎缩可加重胰岛素抵抗并促进糖尿病发展[9], 同时下肢肌肉收缩力量减弱,引起循环血量不足,导致运动耐力降低、呼吸功能减弱等[10-11]。目前对于该病的研究仍以动物实验模型为主,本研究选择GEO数据库中编号为GSE21497的患者骨骼肌样本进行研究,更具客观意义。
通过分析筛选出294个差异基因,经GO分析富集于CC中的差异基因主要存在于肌质、肌膜、肌球蛋白复合物中; MF中差异基因主要参与肌肉构成以及β-连环蛋白、热休克蛋白等物质的结合过程; BP中差异基因主要参与肌肉发育、突触修剪、活性氧代谢等过程。研究[5]发现,肌肉蛋白质的合成和降解失衡、氧化应激反应、自噬等过程在该病的进程中起重要作用。CHEN Z等[12]发现,损伤的肌肉组织中FoxM1转录因子表达量下降,引起Wnt通路中β-连环蛋白信号过度激活,导致肌肉萎缩和再生不良。通过促进FoxM1转录可显著上调肌肉干细胞中Apc的表达,降低β-连环蛋白水平,拮抗肌肉损伤。CRISTOFANI R等[13]发现,小热休克蛋白B8分子通过介导错误折叠蛋白的自噬可缓解肌肉萎缩。
KEGG信号通路中差异基因主要集中在补体系统、FoxO信号通路、谷胱甘肽代谢等通路。研究[14]发现,肌肉损伤后使用重组趋化因子CCL5可促使补体系统C3a和C3aR信号表达增强,促进肌肉再生。FoxOs通路参与体内众多重要生物过程,如自噬、ROS解毒、DNA修复等[15-16]。学者[17]发现,抑制FoxO1、FoxO3、FoxO4基因的激活,可缓解自噬、蛋白降解导致的神经性肌肉萎缩。NINFALI C等[18]学者提出, ZEB1可抑制FoxO3转录活性,从而抑制肌肉萎缩基因Fbxo32和Trim63启动子的转录。ABDULLAH M等[19]通过建立犬肌肉营养不良模型发现,损伤后组织中胶原蛋白纤维化与肌肉萎缩在相关,而脯氨酸/精氨酸代谢途径可能是炎症相关胶原蛋白合成、肌纤维化的核心过程。
通过PPI分析及MCODE算法筛选出18个关键差异基因,其中部分基因已被报道与脊髓损伤后肌肉萎缩过程紧密相关。肌钙蛋白在骨骼肌的收缩过程中起重要作用,脊髓损伤后肌肉组织内源性肌浆网中Ca2+含量降低约10%,与慢速骨骼肌型肌钙蛋白I 1 (TNNI1)的表达相关,通过上调骨骼肌中TNNI1的表达,可增强脊髓损伤者康复运动的抗疲劳性,改善疾病预后[20-22]。肌肉特异性糖原合酶1(GYS1)缺失可导致葡萄糖代谢功能和运动能力受损[23], 促进GYS1上调可提高肌肉收缩能力并减缓萎缩。补体级联反应在神经损伤区域被激活,保护神经免受感染、缓解损害,其具体机制尚未阐明[24-25]。研究[26]证实, C1q、C3、C5等补体在神经损伤后可调控神经再生。此外,肌源性转录因子MYOD1可协同E-box调控肌联蛋白帽(TCAP), 促进对骨骼肌新陈代谢[27]。其余关键差异基因与肌肉萎缩的研究较匮乏,仍需进一步实验探索。
目前,治疗脊髓损伤后肌肉萎缩的方法包括手术、药物、基因工程等[28-31]。早期手术减压可缓解组织继发性缺氧、缺血,降低细胞损伤程度[32-33]。河豚毒素、苯妥英钠等钠通道阻滞剂可维持离子稳态平衡,缓解轴突病变[34-35]。促红细胞生成素上调SDF-1α与G蛋白偶联的CXCR4受体等趋化因子的表达,可募集骨髓间充质干细胞,增强组织抗凋亡能力,改善神经功能等[36-37]。甲泼尼龙等激素可上调抗炎因子、降低组织氧化应激反应、减轻水肿等[38]。学者[39-41]提出,激素治疗不仅在运动或神经功能恢复上与对照组无明显差异,还可能会加重感染、胃肠道出血等症状。胚胎干细胞移植和多能干细胞诱导可调节炎症反应,改变微环境,分泌营养因子,使神经再生[42-44]。
综上所述,本研究所筛选出的差异基因在脊髓损伤病程中涉及微环境变化、神经元变性坏死、肌肉组织纤维化、能量获取、线粒体功能障碍等重要过程。临床可对上述基因的相关机制进行深入研究,以为组织损伤后神经肌肉系统的生长、代谢、凋亡等方面的治疗提供理论依据,从而改善患者预后。
-
表 1 脊髓损伤肌肉萎缩患者第2、5天肌肉样本的差异基因
上调(8个基因) LOC646903、GADD45A、PRRT3-AS1、MSTN、MAP3K7CL、RCSD1、E2F8、LSMEM1 下调(286个基因) TNFRSF18、PRB4、CA9、SEMA5B、GCK、KLRG1、LINC00868、KIAA0040、C16orf71、FAM223B、LOC283194、CSF3、LILRB1、LOC101928111、CA14、LOC101929897、LGALS9、SHISA3、CCDC64B、RTCA、C11orf84、RASSF4、ASPRV1、PORCN、ANKRD34A、MEDAG、LOC101060424、TGM7、BEX4、ST3GAL1、KIF3B、PEX11A、PPARGC1A、F3、XAGE-4、FOXP1-IT1、PARG、HOXC11、CLEC2L、RETSAT、TNFSF13、MYL3、PROCR、ANKRD2、TP53INP2、NEDD4L、NID1、MFAP5、PRKCD、DAXX、FCN3、MYH7、MAP1B、HSD17B11、BBS10、PTPRU、ANGPTL7、SLC27A4、AOX1、FHL5、FABP7、METTL7A、KDR、FAM110D、NDUFC1、RC3H1、KCNB1、SMAP2、CDC37L1、RNF25、NMNAT1、SMAD3、ARID5B、CHN2、SSPN、WBP1L、CYP4B1、CPAMD8、ASAH1、LMCD1、UGP2、ZNF438、C1orf162、PSD、TFPT、ACSM5、COL6A3、RPN1、FAM166B、PDE7A、PIK3CB、DIO2、TSPYL2、SGMS1、MLXIPL、LIX1L、SLC7A2、NMRK2、NCOA3、FEM1C、SMS、MOCOS、VLDLR、FOXO3、LIFR、DDIT4、GPT2、HOMER1、GPX7、MTFP1、EPHB1、TMEM45A、CHAC1、ALOX5AP、SLC19A2、GOT1、PTPRG、SORT1、ITGAM、RASSF1、SLC16A9、LAMB1、P2RY14、MYOM2、PLIN3、ANG、AKR1B10、PRCC、ZBTB16、PIBF1、PKD2、MFGE8、ELF1、LZTS3、HCLS1、THBS2、SLC38A2、METRNL、ECI2、ACSL1、ACTN2、ZNF385B、HSF2、LINC00312、FIBIN、SPSB1、PDK4、SAMD13、CA3、ITGB1BP2、PRKAG3、MT1M、SIRT1、SRPX、NPTX2、ENKD1、C1orf198、LTBP2、YAP1、GPCPD1、FKBP5、FSD2、CPM、CLIC4、FLJ36848、KIAA1161、CNST、ANKRD27、LPIN1、MYOM3、DNAJA4、BLM、MMP3、SLC25A1、RAB23、PRELP、CASQ2、IL1R2、PANK1、PIK3R1、COL5A2、INHBB、ITGA10、ADAMTS5、COL4A1、VIT、RNASE4、CLIC6、ACACB、EBF1、APCDD1、COQ10A、DNAJB5、TSPAN5、BZW1、MYLK4、FBN1、RND3、FOSL2、FAM65B、ROBO1、ANO5、ENPP5、DHRS7C、AGTR1、DHCR24、ANKMY2、GLUL、S100A9、PCYOX1、CD163、IGFBP6、WIPI1、FABP3、RBP4、NFIL3、LINC00948、FAM46C、MIOS、SLC38A1、C5orf27、TNKS1BP1、CNN3、CSPP1、PLAT、C20orf166、SOD2、TMEM208、VCL、SLC2A4、ARHGEF3、GADD45G、LYVE1、SAMHD1、SMAD7、MYL2、GALNT15、SIMC1、SNAI2、FOXO1、HSPA2、SH2D1B、C1QC、TIMP4、VSIG4、MRC1、GGT7、ARG2、RASSF5、SMAD9、IRX3、C1QA、CALML6、SERPINA5、MIR646HG、MYH2、LOC101927391、ABRA、OLFML2A、KLF5、LINC01405、DAAM2、TCAP、IGFBP3、MGST1、RASD1、LINC00844、MAOA、CIDEC、F13A1、GYS1、SLC25A33、C1QB、FBP2、MYOZ2、MAFB、C12orf75、LRRN3、LOC643659、PLTP、CTGF、ECHDC3、FAM179A、PEBP4、TNNC1、TNNI1 -
[1] AHUJA C S, WILSON J R, NORI S, et al. Traumatic spinal cord injury[J]. Nat Rev Dis Primers, 2017, 3: 17018. doi: 10.1038/nrdp.2017.18
[2] NEW P W, BIERING-SØRENSEN F. Review of the history of non-traumatic spinal cord dysfunction[J]. Top Spinal Cord Inj Rehabil, 2017, 23(4): 285-298. doi: 10.1310/sci2304-285
[3] GBD 2016 Traumatic Brain Injury and Spinal Cord Injury Collaborators. Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016[J]. Lancet Neurol, 2019, 18(1): 56-87. doi: 10.1016/S1474-4422(18)30415-0
[4] EBERT SM, AL-ZOUGBI A, BODINE SC, et al. Skeletal Muscle Atrophy: Discovery of Mechanisms and Potential Therapies[J]. Physiology (Bethesda). 2019 Jul 1; 34(4): 232-239.
[5] HYATT H, DEMINICE R, YOSHIHARA T, et al. Mitochondrial dysfunction induces muscle atrophy during prolonged inactivity: a review of the causes and effects[J]. Arch Biochem Biophys, 2019, 662: 49-60. doi: 10.1016/j.abb.2018.11.005
[6] GORGEY A S, KHALIL R E, LESTER R M, et al. Paradigms of lower extremity electrical stimulation training after spinal cord injury[J]. J Vis Exp, 2018(132): 57000. http://europepmc.org/abstract/MED/29443103
[7] CASTRO M J, APPLE D F, HILLEGASS E A, et al. Influence of complete spinal cord injury on skeletal muscle cross-sectional area within the first 6 months of injury[J]. Eur J Appl Physiol Occup Physiol, 1999, 80(4): 373-378. doi: 10.1007/s004210050606
[8] SALTZSTEIN R J, HARDIN S, HASTINGS J. Osteoporosis in spinal cord injury: using an index of mobility and its relationship to bone density[J]. J Am Paraplegia Soc, 1992, 15(4): 232-234. doi: 10.1080/01952307.1992.11761524
[9] NOMURA T, KAWAE T, KATAOKA H, et al. Assessment of lower extremity muscle mass, muscle strength, and exercise therapy in elderly patients with diabetes mellitus[J]. Environ Health Prev Med, 2018, 23(1): 20. doi: 10.1186/s12199-018-0710-7
[10] ITOH M, ENDO M Y, HOJO T, et al. Characteristics of cardiovascular responses to an orthostatic challenge in trained spinal cord-injured individuals[J]. J Physiol Anthropol, 2018, 37(1): 22. doi: 10.1186/s40101-018-0182-x
[11] SASAKI K I, MATSUSE H, AKIMOTO R, et al. Cardiac cycle-synchronized electrical muscle Stimulator for lower limb training with the potential to reduce the heart's pumping workload[J]. PLoS One, 2017, 12(11): e0187395. doi: 10.1371/journal.pone.0187395
[12] CHEN Z, LI L, XU S N, et al. A Cdh1-FoxM1-Apc axis controls muscle development and regeneration[J]. Cell Death Dis, 2020, 11(3): 180. doi: 10.1038/s41419-020-2375-6
[13] CRISTOFANI R, RUSMINI P, GALBIATI M, et al. The regulation of the small heat shock protein B8 in misfolding protein diseases causing motoneuronal and muscle cell death[J]. Front Neurosci, 2019, 13: 796. doi: 10.3389/fnins.2019.00796
[14] ZHANG C C, WANG C X, LI Y L, et al. Complement C3a signaling facilitates skeletal muscle regeneration by regulating monocyte function and trafficking[J]. Nat Commun, 2017, 8(1): 2078. doi: 10.1038/s41467-017-01526-z
[15] LINK W. Introduction to FOXO biology[J]. Methods Mol Biol, 2019, 1890: 1-9. doi: 10.1007/978-1-4939-8900-3_1
[16] BROCCA L, TONIOLO L, REGGIANI C, et al. FoxO-dependent atrogenes vary among catabolic conditions and play a key role in muscle atrophy induced by hindlimb suspension[J]. J Physiol, 2017, 595(4): 1143-1158. doi: 10.1113/JP273097
[17] MILAN G, ROMANELLO V, PESCATORE F, et al. Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy[J]. Nat Commun, 2015, 6: 6670. doi: 10.1038/ncomms7670
[18] NINFALI C, SILES L, DARLING D S, et al. Regulation of muscle atrophy-related genes by the opposing transcriptional activities of ZEB1/CtBP and FOXO3[J]. Nucleic Acids Res, 2018, 46(20): 10697-10708. http://www.researchgate.net/publication/328250385_Regulation_of_muscle_atrophy-related_genes_by_the_opposing_transcriptional_activities_of_ZEB1CtBP_and_FOXO3/download
[19] ABDULLAH M, KORNEGAY J N, HONCOOP A, et al. Non-targeted metabolomics analysis of golden retriever muscular dystrophy-affected muscles reveals alterations in arginine and proline metabolism, and elevations in glutamic and oleic acid in vivo[J]. Metabolites, 2017, 7(3): E38. doi: 10.3390/metabo7030038
[20] SHENG J J, JIN J P. TNNI1, TNNI2 and TNNI3: Evolution, regulation, and protein structure-function relationships[J]. Gene, 2016, 576(1 Pt 3): 385-394. doi: 10.1016/j.gene.2015.10.052
[21] LAMBOLEY C R, WYCKELSMA V L, PERRY BD, et al. Effect of 23-day muscle disuse on sarcoplasmic reticulum Ca2+ properties and contractility in human type I and type II skeletal muscle fibers[J]. J Appl Physiol (1985), 2016, 121(2): 483-492. doi: 10.1152/japplphysiol.00337.2016
[22] CAO T, THONGAM U, JIN J P. Invertebrate troponin: Insights into the evolution and regulation of striated muscle contraction[J]. Arch Biochem Biophys, 2019, 666: 40-45. doi: 10.1016/j.abb.2019.03.013
[23] XIROUCHAKI C E, MANGIAFICO S P, BATE K, et al. Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1(gys1) deletion in adult mice[J]. Mol Metab, 2016, 5(3): 221-232. doi: 10.1016/j.molmet.2016.01.004
[24] DE JONGE R R, VAN SCHAIK I N, VREIJLING J P, et al. Expression of complement components in the peripheral nervous system[J]. Hum Mol Genet, 2004, 13(3): 295-302. http://hmg.oxfordjournals.org/content/13/3/295.full
[25] MCGONIGAL R, CUNNINGHAM M E, YAO D G, et al. C1q-targeted inhibition of the classical complement pathway prevents injury in a novel mouse model of acute motor axonal neuropathy[J]. Acta Neuropathol Commun, 2016, 4: 23. doi: 10.1186/s40478-016-0291-x
[26] LI G S, LI Q F, DONG M M, et al. Complement components of nerve regeneration conditioned fluid influence the microenvironment of nerve regeneration[J]. Neural Regen Res, 2016, 11(4): 682-686. doi: 10.4103/1673-5374.180758
[27] HODGE B A, ZHANG X P, GUTIERREZ-MONREAL M A, et al. MYOD1 functions as a clock amplifier as well as a critical co-factor for downstream circadian gene expression in muscle[J]. Elife, 2019, 8: e43017. doi: 10.7554/eLife.43017
[28] JENDELOVA P. Therapeutic Strategies for Spinal Cord Injury[J]. International Journal of Molecular Sciences, 2018, 19(10): 3200. doi: 10.3390/ijms19103200
[29] KAKABADZE Z, KIPSHIDZE N, MARDALEISHVILI K, et al. Phase 1 trial of autologous bone marrow stem cell transplantation in patients with spinal cord injury[J]. Stem Cells Int, 2016, 2016: 6768274. http://europepmc.org/articles/PMC4940566/
[30] MOORE P D, GORGEY A S, WADE R C, et al. Neuromuscular electrical stimulation and testosterone did not influence heterotopic ossification size after spinal cord injury: a case series[J]. World J Clin Cases, 2016, 4(7): 172-176. doi: 10.12998/wjcc.v4.i7.172
[31] KODANI A, KIKUCHI T, TOHDA C. Acteoside improves muscle atrophy and motor function by inducing new myokine secretion in chronic spinal cord injury[J]. J Neurotrauma, 2019, 36(12): 1935-1948. doi: 10.1089/neu.2018.6000
[32] AHUJA C S, MARTIN A R, FEHLINGS M. Recent advances in managing a spinal cord injury secondary to trauma[J]. F1000Res, 2016, 5: F1000 Faculty Rev-1017. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4890313/
[33] TANAKA C, TAGAMI T, KANEKO J, et al. Early versus late surgery after cervical spinal cord injury: a Japanese nationwide trauma database study[J]. J Orthop Surg Res, 2019, 14(1): 302. doi: 10.1186/s13018-019-1341-4
[34] ROSENBERG L J, TENG Y D, WRATHALL J R. Effects of the sodium channel blocker tetrodotoxin on acute white matter pathology after experimental contusive spinal cord injury[J]. J Neurosci, 1999, 19(14): 6122-6133. doi: 10.1523/JNEUROSCI.19-14-06122.1999
[35] KAPTANOGLU E, SOLAROGLU I, SURUCU H S, et al. Blockade of sodium channels by phenytoin protects ultrastructure and attenuates lipid peroxidation in experimental spinal cord injury[J]. Acta Neurochir (Wien), 2005, 147(4): 405-412. doi: 10.1007/s00701-004-0447-5
[36] LI J, GUO W C, XIONG M, et al. Effect of SDF-1/CXCR4 axis on the migration of transplanted bone mesenchymal stem cells mobilized by erythropoietin toward lesion sites following spinal cord injury[J]. Int J Mol Med, 2015, 36(5): 1205-1214. doi: 10.3892/ijmm.2015.2344
[37] KUCIA M, JANKOWSKI K, RECA R, et al. CXCR4-SDF-1 signalling, locomotion, chemotaxis and adhesion[J]. J Mol Histol, 2004, 35(3): 233-245. http://www.tandfonline.com/servlet/linkout?suffix=CIT0086&dbid=16&doi=10.3109%2F09553002.2014.906766&key=10.1023%2FB%3AHIJO.0000032355.66152.b8
[38] FEHLINGS M G, TETREAULT L A, WILSON J R, et al. A clinical practice guideline for the management of acute spinal cord injury: introduction, rationale, and scope[J]. Global Spine J, 2017, 7(3 Suppl): 84S-94S. http://europepmc.org/articles/PMC5684846/
[39] EVANIEW N, BELLEY-CÔTÉ E P, FALLAH N, et al. Methylprednisolone for the treatment of patients with acute spinal cord injuries: a systematic review and meta-analysis[J]. J Neurotrauma, 2016, 33(5): 468-481. doi: 10.1089/neu.2015.4192
[40] FEHLINGS M G, WILSON J R, HARROP J S, et al. Efficacy and safety of methylprednisolone sodium succinate in acute spinal cord injury: a systematic review[J]. Global Spine J, 2017, 7(3 Suppl): 116S-137S. http://europepmc.org/articles/PMC5684849/
[41] CABRERA-ALDANA E E, RUELAS F, ARANDA C, et al. Methylprednisolone administration following spinal cord injury reduces aquaporin 4 expression and exacerbates edema[J]. Mediators Inflamm, 2017, 2017: 4792932.
[42] GAZDIC M, VOLAREVIC V, HARRELL C R, et al. Stem cells therapy for spinal cord injury[J]. Int J Mol Sci, 2018, 19(4): E1039. doi: 10.3390/ijms19041039
[43] NAGOSHI N, TSUJI O, NAKAMURA M, et al. Cell therapy for spinal cord injury using induced pluripotent stem cells[J]. Regen Ther, 2019, 11: 75-80. doi: 10.1016/j.reth.2019.05.006
[44] JEONG S K, CHOI I, JEON S R. Current status and future strategies to treat spinal cord injury with adult stem cells[J]. J Korean Neurosurg Soc, 2020, 63(2): 153-162. doi: 10.3340/jkns.2019.0146
-
期刊类型引用(3)
1. 肖楚兰,陈泉,万嫣,陈娇娇,赵彤,李柏. 基于转录组测序探究有氧运动改善结直肠癌相关性肌少症的潜在干预机制. 华南预防医学. 2024(09): 786-791+799 . 百度学术
2. 郭恩玉,李自普,王建龙,王文杰,姜山,朱洪峰. 以睡眠相关呼吸功能不全为突出表现的儿童硒蛋白N1相关肌病1例报告. 实用临床医药杂志. 2023(07): 62-66 . 本站查看
3. 邹俊,张继州,蒋畅,韩静. 栝楼桂枝汤通过调节脊髓NMDA受体/ KCC2通路改善脑缺血再灌注大鼠肢体功能. 福建医科大学学报. 2022(02): 111-118 . 百度学术
其他类型引用(1)