动脉粥样硬化炎症相关信号转导通路的研究进展
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摘要
动脉粥样硬化(AS)是各种心脑血管疾病的病理基础,严重威胁着人类的健康,近年来炎症学说受到了越来越多学者的重视,从抗炎及免疫调节角度探讨抗AS是一种新思路,在炎症演变过程中,有多条信号通路参与其中,深入研究信号通路,有望成为动脉粥样硬化药物研究干预靶点。本文从分子生物学水平总结前瞻性的基础研究进展,以期给AS及其相关疾病的治疗带来启发。
Atherosclerosis(AS) is the pathological basis of cardiovascular disease, which is a serious threat to human health. In recent years, more and more scholars pay attention to the theory of inflammation. It is a new idea to treat AS from the point of view with antiinflammation and immunoregulation. There are multiple signal transduction pathways involved in the course of inflammation progress. The signaling pathway is studied deeply that is expected to become a target for intervention of atherosclerosis drugs. This article summerizes the prospective basic experimental from cellular and molecular level, to bring about inspiration in the treatment of AS and AS related diseases.
Atherosclerosis(AS) is the pathological basis of cardiovascular disease, which is a serious threat to human health. In recent years, more and more scholars pay attention to the theory of inflammation. It is a new idea to treat AS from the point of view with antiinflammation and immunoregulation. There are multiple signal transduction pathways involved in the course of inflammation progress. The signaling pathway is studied deeply that is expected to become a target for intervention of atherosclerosis drugs. This article summerizes the prospective basic experimental from cellular and molecular level, to bring about inspiration in the treatment of AS and AS related diseases.
引文
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[2]Libby P.Mechanisms of acute coronary syndromes and their implications for therapy[J].N Engl J Med,2013,368(21):2004-2013.
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[9]Niaudet C,Bonnaud S,Guillonneau M,et al.Plasma membrane reorganization links acid sphingomyelinase/ceramide to p38MAPK pathways in endothelial cells apoptosis[J].Cell Signal,2017,33:10-21.
[10]Cao J,Han Z,Tian L,et al.Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages[J].J Transl Med,2014,12(1):1-10.
[11]张洋,俞博毅,高婷婷,等.罗布麻总黄酮干预p38MAPK/NF-κB信号通路治疗大鼠动脉粥样硬化作用及机制研究[J].吉林医学,2016,37(5):1031-1033.
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[13]Chistiakov DA,Bobryshev YV,Orekhov AN.Macrophagemediated cholesterol handling in Atherosclerosis[J].J Cell Mol Med,2016,20(1):17-28.
[14]Check J,Byrd CL,Menio J.Src kinase partici-pates in LPS-induced activation of NADPH oxidase[J].Mol Immunol,2010,47(4):756-762.
[15]杨蓉,杨莹.巨噬细胞中ox-LDL对TLR4-Src信号通路激活的调控[J].昆明医科大学学报,2017,38(5):44-49.
[16]Lee YG,Lee WM,Kim JY,et al.Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7cells[J].Br J Pharmacol,2008,154(4):852-863.
[17]Schroeter MR,Eschholz N,Herzberg S,et al.Leptin-dependent and leptin-independent paracrine effects of perivascular adipose tissue on neotintima formation[J].Arterioscer Thromb Vasc,2013,33(5):980-987.
[18]Jin ZG,Melaragno MG,廖端芳.Cyclphilin A是一种氧化应激诱导分泌的生长因子[J].中国动脉硬化杂志,2001(2):130.
[19]李敏.亲环素A在大鼠动脉粥样硬化中的作用及其信号传导化制[D].武汉:南方医科大学,2016.
[20]Obinata H,Hla T.Sphingosine 1-phosphate in coagulation and inflamma-tion[J].Semin Immunopathol,2012,34(1):73-91.
[21]王晓楠,周叶,于晓红.瑞舒伐他汀对ox-LDL诱导的内皮细胞损伤中Sphk1/S1P/NF-κB信号通路的影响[J].中国老年学杂志,2017,8(37):1897-1899.
[22]Rosen H,Goetzl EJ.Sphingosine1-phosphate and its receptors:an auto-crine and paracrine network[J].Nat Rev Immunol,2005,5(7):560-570.
[23]Wei J,Lian H,Zhong B,et al.Parafibromin is a component of IFN-gamma-triggered signaling pathways that facilitates JAK1/2-mediated tyrosine phosphorylation of STAT1[J].J Immunol,2015,195(6):2879-2878.
[24]Zhuang G,Wu X,Jiang Z,et al.Tumour-secreted mi R-9promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway[J].EMBO J,2012,31(17):3513-3523.
[25]Dal Monte M,Martini D,Ristori C,et al.Hypoxia effects on proan-giogenic factors in human umbilical vein endothelial cells:functionalrole of the peptide somatostatin[J].Naunyn Schmiedebergs Arch Pharmacol,2011,383(6):593-612.
[26]王和峰,翟纯刚,庞文会,等.PI3K/Akt/m TOR信号通路在巨噬细胞自噬及动脉粥样硬化斑块不稳定中的作用[J].中国病理生理杂志,2013,29(3):390-397.
[27]张志鑫,李彦杰,秦合伟,等.基于PI3K/Akt/m TOR信号通路调控巨噬细胞自噬探讨黄芪甲苷抗动脉粥样硬化的作用机制[J].中草药,2017,48(17):3575-3578.
[28]刘峰,董少红,吴美善,等.紫檀芪通过PI3K-AKT信号途径抑制缺氧/复氧诱导的乳鼠心肌细胞凋亡[J].中国医药科学,2016,6(21):38-41.
[29]李娜,张新庄,王俨如,等.基于网络药理学方法探讨通塞脉片治疗动脉粥样硬化的作用机制[J].中国中药杂志,2016,41(9):1706-1712.
[30]Frutkin AD,Otsuka G,Stempien-Otero A,et al.TGF-[beta]1 limits plaque growth,stabilizes plaque structure,and prevents aortic dilation in apolipoprotein E-null mice[J].Arteriosclerosis,thrombosis,and vascular biology,2009,29(9):1251-1257.
[31]黄江伟,刘厂辉.生长因子β在动脉粥样硬化中作用的研究进展[J].中国医药指南,2013,11(6):58-59.
[32]李翔.基于TGF-/Smad通路ATRA改善早期颈动脉粥样硬化的作用机制[D].广州:广东药学院,2015.
[33]刘杨,全翊宁,王新春,等.香青兰总黄酮对Apo E-/-小鼠动脉粥样硬化病变中TGF-β1/Smad信号通路及基质金属蛋白酶表达的影响[J].中国中药杂志,2017,42(14):2744-2747.
[34]Ierardi E,Sorrentino C,Principi M,et al.Intestinal microbial metabolism of phosphatidy lcholine:a novel insight in the cardiovascular risk scenario[J].Hepatobiliary Surg Nutr,2015,4(4):289-292.
[35]Martínez-Del Campo A,Romano KA,Rey FE,et al.The plot thickens:diet microbe interactions may modulate thrombosis risk[J].Cell Metab,2016,23(4):573-575.
[36]Yin J,Liao SX,He Y,et al.Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack[J].J Am Heart Assoc,2015,4(11):e002699.
[37]Schugar RC,Brown JM.Emerging roles of flavin monooxygenase 3 in cholesterol metabolism and atherosclerosis[J].Curr Opin Lipidol,2015,26(5):426-431.
[38]Spector R.New insight into the cause of atherosclerosis:implications for pharmacology[J].J Pharmacol Exp Ther,2016,358(1):103-108.
[2]Libby P.Mechanisms of acute coronary syndromes and their implications for therapy[J].N Engl J Med,2013,368(21):2004-2013.
[3]Edfeldt K,Swedenborg J,Hansson GK,et al.Expression of toll-like receptors in human atherosclerotic lesions:a possible pathway for plaque activation[J].Circulation,2002,105(10):1158-1161.
[4]杨燕燕,谢金东,俞春英,等.TLR4信号通路在中药抗动脉粥样硬化中的研究进展[C].福州:福建中医药大学,2014.
[5]Pamukcu B,Lip GY,Shantsila E.The nuclear factor-kappa B pathway in a therosclerosis:a potential therapeutic target for atherothrombotic vascular disease[J].Thrombosis research,2011,128(2):117-123.
[6]Takeuchi O,Takeda K,Hoshino K,et al.Cellular responses to bacterial cell wall components are mediated through My D88-dependent signaling cascades[J].Int Immunol,2000,12(1):113-117.
[7]Zhang LB,Man ZT,Li W,et al.Calcitonin protects chondro-cytes from lipopolysaccharide-induced apoptosis and inflammatoryresponse through MAPK/Wnt/NF-κB pathways[J].Mol Immunol,2017,87:249-257.
[8]Shin MH,Choi JS,Rhee JA,et al.APOE,polymorphism and carotid atherosclerosis in Korean population:the dong-gu study and the namwon study[J].Atherosclerosis,2014,232(1):180-185.
[9]Niaudet C,Bonnaud S,Guillonneau M,et al.Plasma membrane reorganization links acid sphingomyelinase/ceramide to p38MAPK pathways in endothelial cells apoptosis[J].Cell Signal,2017,33:10-21.
[10]Cao J,Han Z,Tian L,et al.Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages[J].J Transl Med,2014,12(1):1-10.
[11]张洋,俞博毅,高婷婷,等.罗布麻总黄酮干预p38MAPK/NF-κB信号通路治疗大鼠动脉粥样硬化作用及机制研究[J].吉林医学,2016,37(5):1031-1033.
[12]Sun CH,Wu MH,Lee ES,et al.A disintegrin and metallo-proteinase 15 contributes to atherosclerosis by mediating endothelial barrier dysfunction via Src family kinase activity[J].Arterioscler Thromb Vasc Biol,2012,32(10):2444-2451.
[13]Chistiakov DA,Bobryshev YV,Orekhov AN.Macrophagemediated cholesterol handling in Atherosclerosis[J].J Cell Mol Med,2016,20(1):17-28.
[14]Check J,Byrd CL,Menio J.Src kinase partici-pates in LPS-induced activation of NADPH oxidase[J].Mol Immunol,2010,47(4):756-762.
[15]杨蓉,杨莹.巨噬细胞中ox-LDL对TLR4-Src信号通路激活的调控[J].昆明医科大学学报,2017,38(5):44-49.
[16]Lee YG,Lee WM,Kim JY,et al.Src kinase-targeted anti-inflammatory activity of davallialactone from Inonotus xeranticus in lipopolysaccharide-activated RAW264.7cells[J].Br J Pharmacol,2008,154(4):852-863.
[17]Schroeter MR,Eschholz N,Herzberg S,et al.Leptin-dependent and leptin-independent paracrine effects of perivascular adipose tissue on neotintima formation[J].Arterioscer Thromb Vasc,2013,33(5):980-987.
[18]Jin ZG,Melaragno MG,廖端芳.Cyclphilin A是一种氧化应激诱导分泌的生长因子[J].中国动脉硬化杂志,2001(2):130.
[19]李敏.亲环素A在大鼠动脉粥样硬化中的作用及其信号传导化制[D].武汉:南方医科大学,2016.
[20]Obinata H,Hla T.Sphingosine 1-phosphate in coagulation and inflamma-tion[J].Semin Immunopathol,2012,34(1):73-91.
[21]王晓楠,周叶,于晓红.瑞舒伐他汀对ox-LDL诱导的内皮细胞损伤中Sphk1/S1P/NF-κB信号通路的影响[J].中国老年学杂志,2017,8(37):1897-1899.
[22]Rosen H,Goetzl EJ.Sphingosine1-phosphate and its receptors:an auto-crine and paracrine network[J].Nat Rev Immunol,2005,5(7):560-570.
[23]Wei J,Lian H,Zhong B,et al.Parafibromin is a component of IFN-gamma-triggered signaling pathways that facilitates JAK1/2-mediated tyrosine phosphorylation of STAT1[J].J Immunol,2015,195(6):2879-2878.
[24]Zhuang G,Wu X,Jiang Z,et al.Tumour-secreted mi R-9promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway[J].EMBO J,2012,31(17):3513-3523.
[25]Dal Monte M,Martini D,Ristori C,et al.Hypoxia effects on proan-giogenic factors in human umbilical vein endothelial cells:functionalrole of the peptide somatostatin[J].Naunyn Schmiedebergs Arch Pharmacol,2011,383(6):593-612.
[26]王和峰,翟纯刚,庞文会,等.PI3K/Akt/m TOR信号通路在巨噬细胞自噬及动脉粥样硬化斑块不稳定中的作用[J].中国病理生理杂志,2013,29(3):390-397.
[27]张志鑫,李彦杰,秦合伟,等.基于PI3K/Akt/m TOR信号通路调控巨噬细胞自噬探讨黄芪甲苷抗动脉粥样硬化的作用机制[J].中草药,2017,48(17):3575-3578.
[28]刘峰,董少红,吴美善,等.紫檀芪通过PI3K-AKT信号途径抑制缺氧/复氧诱导的乳鼠心肌细胞凋亡[J].中国医药科学,2016,6(21):38-41.
[29]李娜,张新庄,王俨如,等.基于网络药理学方法探讨通塞脉片治疗动脉粥样硬化的作用机制[J].中国中药杂志,2016,41(9):1706-1712.
[30]Frutkin AD,Otsuka G,Stempien-Otero A,et al.TGF-[beta]1 limits plaque growth,stabilizes plaque structure,and prevents aortic dilation in apolipoprotein E-null mice[J].Arteriosclerosis,thrombosis,and vascular biology,2009,29(9):1251-1257.
[31]黄江伟,刘厂辉.生长因子β在动脉粥样硬化中作用的研究进展[J].中国医药指南,2013,11(6):58-59.
[32]李翔.基于TGF-/Smad通路ATRA改善早期颈动脉粥样硬化的作用机制[D].广州:广东药学院,2015.
[33]刘杨,全翊宁,王新春,等.香青兰总黄酮对Apo E-/-小鼠动脉粥样硬化病变中TGF-β1/Smad信号通路及基质金属蛋白酶表达的影响[J].中国中药杂志,2017,42(14):2744-2747.
[34]Ierardi E,Sorrentino C,Principi M,et al.Intestinal microbial metabolism of phosphatidy lcholine:a novel insight in the cardiovascular risk scenario[J].Hepatobiliary Surg Nutr,2015,4(4):289-292.
[35]Martínez-Del Campo A,Romano KA,Rey FE,et al.The plot thickens:diet microbe interactions may modulate thrombosis risk[J].Cell Metab,2016,23(4):573-575.
[36]Yin J,Liao SX,He Y,et al.Dysbiosis of gut microbiota with reduced trimethylamine-N-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack[J].J Am Heart Assoc,2015,4(11):e002699.
[37]Schugar RC,Brown JM.Emerging roles of flavin monooxygenase 3 in cholesterol metabolism and atherosclerosis[J].Curr Opin Lipidol,2015,26(5):426-431.
[38]Spector R.New insight into the cause of atherosclerosis:implications for pharmacology[J].J Pharmacol Exp Ther,2016,358(1):103-108.