基于系统生物学的针灸治疗中风潜在作用机制探讨
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摘要
目的:通过系统生物学方法探讨针灸治疗中风的潜在作用机制。方法:系统检索PubMed、 Embase、Cochrane Library、中国生物医学文摘数据库(CBM)、中国期刊全文数据库(CNKI)、中文科技期刊数据库(VIP)和万方数据库(WanFang),收集关于针灸治疗中风机制的实验研究文献,从符合纳入标准的文献中筛选出与针灸治疗中风机制相关的靶标、基因和通路;利用STRING在线数据库对靶标进行蛋白质与蛋白质相互作用(PPI)网络的构建与分析;从Uniprot数据库中获取靶标蛋白的基因名称后,借助DAVID数据库进基因本体(GO)功能分析和KEGG通路富集分析,研究针灸治疗中风的作用机制。结果:PPI网络图结果表明针灸治疗中风的核心靶标有IL8、TNF、IL6、IL1B、ICAM1、C3、POMC、PTGS2、CRP、NPY等;GO分析结果表明针灸治疗中风的作用主要通过干预炎症反应、白细胞介素-8生产的正调节、细胞凋亡的积极调节等发挥生物学功能;KEGG结果表明针灸治疗中风主要作用与TNF signaling pathway、NF-kappa B signaling pathway、MAPK signaling pathway、NOD-like receptor signaling pathway、Adipocytokine signaling pathway等信号通路有关。结论:由此可见,针灸主要通过抑制炎症反应、细胞凋亡和补体激活等多种途径、多种信号通路来发挥其治疗中风的作用。
Objective:To investigate the potential mechanism of acupuncture treatment for stroke based on systems biology.Methods:To retrieval PubMed,Embase,the Cochrane Library,the Chinese biomedical abstract database(CBM),China journal full-text database(CNKI),Chinese science and technology periodical database(VIP) and WanFang database systematically,we collected experimental literature about acupuncture treatment for stroke mechanism.Targets,genes and pathways from standard literature related to acupuncture treatment for stroke mechanism was selected.STRING online database was used to build and analyze protein-protein interaction(PPI) networks.The gene name of target protein was obtained from the uniprot database,and then with the help of DAVID database,the gene ontology(GO) analysis,clustering analysis and KEGG pathway enrichment analysis were carried out.Results:The PPI network diagram results indicated that the core target of acupuncture treatment for stroke are as follows:IL8,TNF,IL6,IL1 B,ICAM1,C3,POMC,PTGS2,CRP,NPY,etc.GO analysis indicated that acupuncture treated stroke mainly through the intervening inflammation,positive regulation of interleukin-8 production,positive regulation of apoptotic cell clearance and other biological functions.KEGG results showed that the main effect of acupuncture therapy for stroke was related to TNF signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway,NOD-like receptor signaling pathway,adipocytokine signaling pathway and so on.Conclusion:Therefore,acupuncture mainly treats stroke through a variety of channels,a variety of signaling pathways,such as inhibiting the inflammatory response,apoptosis and complement activation and so on.
Objective:To investigate the potential mechanism of acupuncture treatment for stroke based on systems biology.Methods:To retrieval PubMed,Embase,the Cochrane Library,the Chinese biomedical abstract database(CBM),China journal full-text database(CNKI),Chinese science and technology periodical database(VIP) and WanFang database systematically,we collected experimental literature about acupuncture treatment for stroke mechanism.Targets,genes and pathways from standard literature related to acupuncture treatment for stroke mechanism was selected.STRING online database was used to build and analyze protein-protein interaction(PPI) networks.The gene name of target protein was obtained from the uniprot database,and then with the help of DAVID database,the gene ontology(GO) analysis,clustering analysis and KEGG pathway enrichment analysis were carried out.Results:The PPI network diagram results indicated that the core target of acupuncture treatment for stroke are as follows:IL8,TNF,IL6,IL1 B,ICAM1,C3,POMC,PTGS2,CRP,NPY,etc.GO analysis indicated that acupuncture treated stroke mainly through the intervening inflammation,positive regulation of interleukin-8 production,positive regulation of apoptotic cell clearance and other biological functions.KEGG results showed that the main effect of acupuncture therapy for stroke was related to TNF signaling pathway,NF-kappa B signaling pathway,MAPK signaling pathway,NOD-like receptor signaling pathway,adipocytokine signaling pathway and so on.Conclusion:Therefore,acupuncture mainly treats stroke through a variety of channels,a variety of signaling pathways,such as inhibiting the inflammatory response,apoptosis and complement activation and so on.
引文
[1] 张琳瑛.中风的针灸治疗概况[J].针灸临床杂志,2004,20(6):61-62.
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[3] Verpoorte R,Crommelin D,Danhof M,et al.A systems view on the future of medicine:Inspiration from Chinese medicine[J].Journal of Ethnopharmacology,2009,121(3):479-481.
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[12] 孔立红,曾晓玲,任婕.电针对脑缺血再灌注大鼠海马细胞因子TNF-α、IL-6含量的影响[J].中华现代中西医杂志,2006,16(2):97.
[13] 李丹丹,马茜,王辛,等.IL-1β在缺血性脑卒中发病中的作用机制研究进展[J].山东医药,2015,45(35):91-93.
[14] 赖文芳,张小琴,洪海棉,等.红景天苷对大鼠局灶性脑缺血/再灌注损伤的神经保护作用[J].中国药理学通报,2015,54(6):775-780.
[15] 许元丰.疏血通注射液联合醒脑静注射液治疗急性缺血性脑卒中50例[J].河南中医,2015,35(12):2955-2956.
[16] 朱文斌,刘运海,杨期东,等.载脂蛋白JmRNA在大鼠脑梗死模型中的表达[J].卒中与神经疾病,2004,11(6):329-332.
[17] 郭景瑞,朱传英,王敏.急性脑梗死患者血清C反应蛋白与C_3水平变化及意义[J].山东医药,2008,48(44):39-41.
[18] 刘文杰,刘晓松,杜艳华.益气活血通络方联合低分子肝素治疗气虚血瘀证缺血性脑卒中患者肌力恢复55例[J].中国实验方剂学杂志,2015,21(14):149-152.
[19] 张静,芮耀诚,杨鹏远,等.药物对C反应蛋白诱导脑微血管内皮细胞黏附分子表达的作用[J].中国微循环,2008,12(4):219-221.
[20] 徐士欣,张军平,朱亚萍,等.舒脑欣滴丸对急性缺血性中风患者血清补体C3、C4及炎症指标的影响[J].中华中医药学刊,2013,34(9):1968-1970.
[21] 杜丹华,吴江,高鹏,等.环氧合酶基因多态性与缺血性卒中相关性研究[J].中风与神经疾病,2008,25(1):49-52.
[22] Yamamoto S,Matsui K,Ohashi N.Protective effect of Na+/H+ exchange inhibitor,SM-20550,on impaired mitochondrial respiratory function and mitochondrial Ca2+ overload in ischemic/reperfused rat hearts.[J].Journal of Cardiovascular Pharmacology,2002,39(4):569.
[23] Demasi M,Cleland L G,Cookjohnson R J,et al.Effects of Hypoxia on Monocyte Inflammatory Mediator Production DISSOCIATION BETWEEN CHANGES IN CYCLOOXYGENASE-2 EXPRESSION AND EICOSANOID SYNTHESIS[J].Journal of Biological Chemistry,2003,278(40):38607-38616.
[24] 王玉,杨洁红,何昱,等.养阴通脑颗粒对大鼠脑缺血/再灌注损伤的保护作用及其抑制NF-κB信号通路的作用机制[J].中华中医药杂志,2017,32(8):3713-3717.
[25] 万强.内脏脂肪素激活MAPKs通路参与动脉粥样硬化形成及小檗碱的干预研究[D].广州:南方医科大学,2014.
[26] 鲁敏晔,宋水江.脑梗死患者血清C3,C4水平的变化[C]//浙江省神经病学学术年会,2008.
[27] 方永军,胡亚莉,张毅,等.大黄对高血压脑出血术后患者血清补体C3、C4的影响[J].中西医结合心脑血管病杂志,2011,9(9):1075-1076.
[2] 管遵惠.针灸治疗中风病的研究进展及展望[J].云南中医学院学报,2006,29(1):52-54.
[3] Verpoorte R,Crommelin D,Danhof M,et al.A systems view on the future of medicine:Inspiration from Chinese medicine[J].Journal of Ethnopharmacology,2009,121(3):479-481.
[4] Woodruff T M,Thundyil J,Tang S C,et al.Pathophysiology,treatment,and animal and cellular models of human ischemic stroke.[J].Molecular Neurodegeneration,2011,6(1):1-19.
[5] Wu Z,Yao C,Zhao D,et al.Sino-MONICA Project A Collaborative Study on Trends and Determinants in Cardiovascular Diseases in China,Part I:Morbidity and Mortality Monitoring[J].Circulation,2001,103(3):462.
[6] 张予阳,刘岩,付守廷.脑缺血与炎症反应[J].中国药理学通报,2006,22(1):5-9.
[7] 丁永忠,孙群周,张建生.急性颅脑损伤后血清TNF-α,IL-1,IL-6,IL-8含量变化及其临床意义[J].中国临床神经外科杂志,2006,11(1):17-19.
[8] 刘恒方,高灵利,王建平,等.脂联素、肿瘤坏死因子-α、白介素-6与人颈动脉粥样硬化斑块关系的研究[J].中华神经医学杂志,2014,13(2):151-155.
[9] 高灵利.APN、TNF-α、IL-6与人颈动脉粥样硬化斑块关系的研究[D].郑州:郑州大学,2014.
[10] 王政,赵会忠,陈红丽,等.急性冠脉综合征患者血清MMP-2、MMP-9及IL-6水平的检测及其临床意义[J].中国当代医药,2014(22):4-6.
[11] Offner H,Subramanian S,Parker S M,et al.Experimental stroke induces massive,rapid activation of the peripheral immune system[J].Journal of Cerebral Blood Flow & Metabolism Official Journal of the International Society of Cerebral Blood Flow & Metabolism,2006,26(5):654.
[12] 孔立红,曾晓玲,任婕.电针对脑缺血再灌注大鼠海马细胞因子TNF-α、IL-6含量的影响[J].中华现代中西医杂志,2006,16(2):97.
[13] 李丹丹,马茜,王辛,等.IL-1β在缺血性脑卒中发病中的作用机制研究进展[J].山东医药,2015,45(35):91-93.
[14] 赖文芳,张小琴,洪海棉,等.红景天苷对大鼠局灶性脑缺血/再灌注损伤的神经保护作用[J].中国药理学通报,2015,54(6):775-780.
[15] 许元丰.疏血通注射液联合醒脑静注射液治疗急性缺血性脑卒中50例[J].河南中医,2015,35(12):2955-2956.
[16] 朱文斌,刘运海,杨期东,等.载脂蛋白JmRNA在大鼠脑梗死模型中的表达[J].卒中与神经疾病,2004,11(6):329-332.
[17] 郭景瑞,朱传英,王敏.急性脑梗死患者血清C反应蛋白与C_3水平变化及意义[J].山东医药,2008,48(44):39-41.
[18] 刘文杰,刘晓松,杜艳华.益气活血通络方联合低分子肝素治疗气虚血瘀证缺血性脑卒中患者肌力恢复55例[J].中国实验方剂学杂志,2015,21(14):149-152.
[19] 张静,芮耀诚,杨鹏远,等.药物对C反应蛋白诱导脑微血管内皮细胞黏附分子表达的作用[J].中国微循环,2008,12(4):219-221.
[20] 徐士欣,张军平,朱亚萍,等.舒脑欣滴丸对急性缺血性中风患者血清补体C3、C4及炎症指标的影响[J].中华中医药学刊,2013,34(9):1968-1970.
[21] 杜丹华,吴江,高鹏,等.环氧合酶基因多态性与缺血性卒中相关性研究[J].中风与神经疾病,2008,25(1):49-52.
[22] Yamamoto S,Matsui K,Ohashi N.Protective effect of Na+/H+ exchange inhibitor,SM-20550,on impaired mitochondrial respiratory function and mitochondrial Ca2+ overload in ischemic/reperfused rat hearts.[J].Journal of Cardiovascular Pharmacology,2002,39(4):569.
[23] Demasi M,Cleland L G,Cookjohnson R J,et al.Effects of Hypoxia on Monocyte Inflammatory Mediator Production DISSOCIATION BETWEEN CHANGES IN CYCLOOXYGENASE-2 EXPRESSION AND EICOSANOID SYNTHESIS[J].Journal of Biological Chemistry,2003,278(40):38607-38616.
[24] 王玉,杨洁红,何昱,等.养阴通脑颗粒对大鼠脑缺血/再灌注损伤的保护作用及其抑制NF-κB信号通路的作用机制[J].中华中医药杂志,2017,32(8):3713-3717.
[25] 万强.内脏脂肪素激活MAPKs通路参与动脉粥样硬化形成及小檗碱的干预研究[D].广州:南方医科大学,2014.
[26] 鲁敏晔,宋水江.脑梗死患者血清C3,C4水平的变化[C]//浙江省神经病学学术年会,2008.
[27] 方永军,胡亚莉,张毅,等.大黄对高血压脑出血术后患者血清补体C3、C4的影响[J].中西医结合心脑血管病杂志,2011,9(9):1075-1076.
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