南蛇藤素抗动脉粥样硬化机制的研究进展
|
摘要
动脉粥样硬化(As)是心血管系统疾病中的常见疾病。As的病理生理基础为内膜的脂质累积、纤维组织增生、钙质沉着,继发斑块内出血、斑块破裂、局部血栓形成,最终导致急性心脑血管事件。而在抗As方面,中药的某些成分较西药有更低的毒性和更好的药物耐受性,其中南蛇藤素作用显著。南蛇藤素是一种具有多种生物活性的天然物质,有良好的药理活性。其主要从抑制炎症反应、调节脂质代谢、保护血管内皮细胞等方面发挥作用。未来,对南蛇藤素进行深入研究有利于开发更有针对性的As药物靶点。
Atherosclerosis( As) is a common disease in cardiovascular system. The pathological and physiological basis of As is the accumulation of lipids in the intima,hyperplasia of fibrous tissue,calcinosis,and secondary hemorrhage in plaques,plaque rupture,local thrombosis,ultimately leading to acute cardiovascular and cerebrovascular events. As for anti-As,some components of traditional Chinese medicine have lower toxicity and better drug tolerance than western medicine,among which celastrol has a significant effect. Celastrol is a natural substance with many biological activities and has good pharmacological effects. It plays an important role in inhibiting inflammation,regulating lipid metabolism and protecting vascular endothelial cells. In the future,in-depth research on celastrol will be conducive to the development of more As drug targets.
Atherosclerosis( As) is a common disease in cardiovascular system. The pathological and physiological basis of As is the accumulation of lipids in the intima,hyperplasia of fibrous tissue,calcinosis,and secondary hemorrhage in plaques,plaque rupture,local thrombosis,ultimately leading to acute cardiovascular and cerebrovascular events. As for anti-As,some components of traditional Chinese medicine have lower toxicity and better drug tolerance than western medicine,among which celastrol has a significant effect. Celastrol is a natural substance with many biological activities and has good pharmacological effects. It plays an important role in inhibiting inflammation,regulating lipid metabolism and protecting vascular endothelial cells. In the future,in-depth research on celastrol will be conducive to the development of more As drug targets.
引文
[1] Pant S,Deshmukh A,Gurumurthy GS,et al. Inflammation and atherosclerosis—revisited[J]. J Cardiovasc Pharmacol Ther,2014,19(2):170-178.
[2]陈瑗,周玫.氧化应激-炎症在动脉粥样硬化发生发展中作用研究的新进展[J].中国动脉硬化杂志,2008,16(10):757-762.
[3]阎雨,何阳阳,方莲花,等.巨噬细胞在动脉粥样硬化中的研究进展[J].中国药学杂志,2014,49(1):7-10.
[4] Kusters PJ,Lutgens E. Cytokines and Immune Responses in Murine Atherosclerosis[J]. Methods Mol Biol,2015,1339:17-40.
[5]钟点,陈渊,赵伟.雷公藤红素抗炎及免疫抑制的研究进展[J].药物生物技术,2018,25(1):64-69.
[6] Zhang J,Shan J,Chen X,et al. Celastrol mediates Th17 and Treg cell generation via metabolic signaling[J]. Biochem Biophys Res Commun,2018,497(3):883-889.
[7] Han XB,Tan Y,Fang YQ,et al. Protective effects of celastrol againstγirradiation-induced oxidative stress in human umbilical vein endothelial cells[J]. Exp Ther Med,2018,16(2):685-694.
[8] Ma L,Peng L,Fang S,et al. Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma Hep G2 cells[J]. Oncol Rep,2017,38(5):2951-2958.
[9] Zhu F,Li C,Jin XP,et al. Celastrol may have an anti-atherosclerosis effect in a rabbit experimental carotid atherosclerosis model[J].Int J Clin Exp Med,2014,7(7):1684-1691.
[10] Ross R. Atherosclerosis—an inflammatory disease[J]. N Engl J Med,1999,340(2):115-126.
[11]刘俊田.动脉粥样硬化发病的炎症机制的研究进展[J].西安交通大学学报(医学版),2015,36(2):141-152.
[12] Zhang B,Wu T,Chen M,et al. The CD40/CD40L system:A new therapeutic target for disease[J]. Immunol Lett,2013,153(1/2):58-61.
[13]薛凌,邱雅慧,张扬,等. CD40-CD40配体系统对兔动脉粥样硬化形成的影响[J].现代预防医学,2012,39(13):3318-3321.
[14] Lutgens E,Cleutjens KB,Heeneman S,et al. Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype[J]. Proc Natl Acad Sci U S A,2000,97(13):7464-7469.
[15]程军,李金平,田卓,等.南蛇藤素对ApoE基因敲除小鼠主动脉粥样硬化斑块内CD40配体表达、巨噬细胞和平滑肌细胞数量的影响[J].中国病理生理杂志,2009,25(3):601-603.
[16] Thiele JR,Zeller J,Bannasch H,et al. Targeting C-reactive protein in inflammatory disease by preventing conformational changes[J]. Mediators Inflamm,2015,2015:372432.
[17] Stancel N,Chen CC,Ke LY,et al. Interplay between CRP,Atherogenic LDL,and LOX-1 and its potential role in the pathogenesis of atherosclerosis[J]. Clin Chem,2016,62(2):320-327.
[18] Pasceri V,Willerson JT,Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells[J]. Circulation,2000,102(18):2165-2168.
[19]徐艳杰,程晓曙. C反应蛋白与动脉粥样硬化[J].生命科学,2012,24(5):450-455.
[20]程军,李金平,田卓,等.南蛇藤素对载脂蛋白E基因敲除小鼠主动脉壁C反应蛋白及组织因子表达的影响[J].中国动脉硬化杂志,2008,16(5):341-344.
[21] Gong Z,Xing S,Zheng F,et al. Increased expression of macrophage migration inhibitory factor in aorta of patients with coronary atherosclerosis[J]. J Cardiovasc Surg(Torino),2015,56(4):631-637.
[22]储莉,刘伏元,王烈成.巨噬细胞移动抑制因子与动脉粥样硬化的相关性[J].广东医学,2015,36(5):680-682.
[23]徐斌,尹彤,赵玉生.巨噬细胞移动抑制因子在动脉粥样硬化中的作用研究进展[J].中国动脉硬化杂志,2004,12(2):238-240.
[24]杨瑞芳,阴彦龙,杨敏清,等.基质金属蛋白酶与动脉粥样硬化及斑块破裂的关系[J].分子影像学杂志,2017,40(4):482-485.
[25] Deleon-Pennell KY,Altara R,Yabluchanskiy A,et al. The circular relationship between matrix metalloproteinase-9 and inflammation following myocardial infarction[J]. IUBMB Life,2015,67(8):611-618.
[26] Kurzepa J,Madro A,Czechowska G,et al. Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis,chronic pancreatitis and non-specific inflammatory bowel diseases[J]. Hepatobiliary Pancreat Dis Int,2014,13(6):570-579.
[27] Galis ZS,Sukhova GK,Lark MW,et al. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques[J]. J Clin Invest,1994,94(6):2493-2503.
[28]李金平,程军,田卓,等.南蛇藤素对ApoE基因敲除小鼠主动脉壁MIF及MMP-9表达的影响[J].第三军医大学学报,2008,30(9):827-830.
[29]欧思琳,李茹冰. NF-κB在动脉粥样硬化疾病中的研究进展[J].中国免疫学杂志,2018,34(7):1095-1101.
[30] Lenardo MJ,Baltimore D. NF-kappa B:A pleiotropic mediator of inducible and tissue-specific gene control[J]. Cell,1989,58(2):227-229.
[31] Wang Y,Wang X,Sun M,et al. NF-κB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell[J]. Biochem Biophys Res Commun,2011,411(3):543-548.
[32] Pateras I,Giaginis C,Tsigris C,et al. NF-κB signaling at the crossroads of inflammation and atherogenesis:Searching for new therapeutic links[J]. Expert Opin Ther Targets,2014,18(9):1089-1101.
[33] Li Q,Syrovets T,Simmet T,et al. Plasmin induces intercellular adhesion molecule 1 expression in human endothelial cells via nuclear factor-κB/mitogen-activated protein kinases-dependent pathways[J]. Exp Biol Med(Maywood),2013,238(2):176-186.
[34] Gu L,Bai WL,Li S,et al. Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress[J]. PLo S One,2013,8(6):e65477.
[35]赖平.脂质在动脉粥样硬化早期病理变化过程中作用的研究进展[J].赣南医学院学报,2017,37(6):995-1000.
[36] Gluba-Brzózka A,Franczyk B,Banach M,et al. Do HDL and LDL subfractions play a role in atherosclerosis in end-stage renal disease(ESRD)patients?[J]. Int Urol Nephrol,2017,49(1):155-164.
[37] Bandeali S,Farmer J. High-density lipop-rotein and atherosclerosis:The role of antioxidant activity[J]. Curr Atheroscler Rep,2012,14(2):101-107.
[38]张颖.南蛇藤生物活性成分分析及其抗动脉粥样硬化药效评价[D].济南:山东农业大学,2013.
[39] Sawamura T,Kume N,Aoyama T,et al. An endothelial receptor for oxidized low-density lipoprotein[J]. Nature,1997,386(6620):73-77.
[40]郑旭,张梦诃,邓姣,等. LOX-1在动脉粥样硬化中的作用研究新进展[J].心脏杂志,2018,30(2):212-217.
[41] Kataoka H,Kume N,Miyamoto S,et al. Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions[J]. Circulation,1999,99(24):3110-3117.
[42] Li DY,Chen HJ,Mehta JL. Statins inhibit oxidized-LDL-mediated LOX-1 expression,uptake of oxidized-LDL and reduction in PKB phosphorylation[J]. Cardiovasc Res,2001,52(1):130-135.
[43] Gimbrone MA Jr,García-Carde1a G. Endothelial cell dysfunction and the pathobiology of atherosclerosis[J]. Circ Res,2016,118(4):620-636.
[44]林艾雯,陈竹君.动脉粥样硬化与内皮细胞损伤机制的研究进展[J].岭南心血管病杂志,2015,21(4):580-582.
[45] Asahara T,Murohara T,Sullivan A,et al. Isolation of putative progenitor endothelial cells for angiogenesis[J]. Science,1997,275(5302):964-967.
[46] Huang S,Tang Y,Cai X,et al. Celastrol inhibits vasculogenesis by suppressing the VEGF-induced functional activity of bone marrow-derived endothelial progenitor cells[J]. Biochem Biophys Res Commun,2012,423(3):467-472.
[47] Lu C,Yu X,Zuo K,et al. Tripterine treatment improves endothelial progenitor cell function via integrin-linked kinase[J]. Cell Physiol Biochem,2015,37(3):1089-1103.
[48]张世田,唐汉庆,黄岑汉,等.氧化应激、炎症与冠状动脉粥样硬化关系的研究进展[J].右江医学,2017,45(2):235-239.
[49] Chen K,Keaney JF Jr. Evolving concepts of oxidative stress and reactive oxygen species in cardiovascular disease[J]. Curr Atheroscler Rep,2012,14(5):476-483.
[50] Zhu H,Jin X,Zhao J,et al. Probucol protects against atherosclerosis through lipid-lowering and suppressing immune maturation of CD11c+dendritic cells in STZ-induced diabetic LDLR-/-mice[J].J Cardiovasc Pharmacol,2015,65(6):620-627.
[51] Suzuki-Inoue K. Activation and inhibitory mechanisms of blood platelets[J]. Nihon Rinsho,2014,72(7):1212-1217.
[52] Franco AT,Corken A,Ware J. Platelets at the interface of thrombosis,inflammation,and cancer[J]. Blood,2015,126(5):582-588.
[53] Duchene J,von Hundelshausen P. Platelet-derived chemokines in atherosclerosis[J]. Hamostaseologie,2015,35(2):137-141.
[54]李金平.南蛇藤素对血小板功能及Apo E-/-小鼠动脉壁MIF、MMP-9表达的影响[D].重庆:第三军医大学,2008.
[2]陈瑗,周玫.氧化应激-炎症在动脉粥样硬化发生发展中作用研究的新进展[J].中国动脉硬化杂志,2008,16(10):757-762.
[3]阎雨,何阳阳,方莲花,等.巨噬细胞在动脉粥样硬化中的研究进展[J].中国药学杂志,2014,49(1):7-10.
[4] Kusters PJ,Lutgens E. Cytokines and Immune Responses in Murine Atherosclerosis[J]. Methods Mol Biol,2015,1339:17-40.
[5]钟点,陈渊,赵伟.雷公藤红素抗炎及免疫抑制的研究进展[J].药物生物技术,2018,25(1):64-69.
[6] Zhang J,Shan J,Chen X,et al. Celastrol mediates Th17 and Treg cell generation via metabolic signaling[J]. Biochem Biophys Res Commun,2018,497(3):883-889.
[7] Han XB,Tan Y,Fang YQ,et al. Protective effects of celastrol againstγirradiation-induced oxidative stress in human umbilical vein endothelial cells[J]. Exp Ther Med,2018,16(2):685-694.
[8] Ma L,Peng L,Fang S,et al. Celastrol downregulates E2F1 to induce growth inhibitory effects in hepatocellular carcinoma Hep G2 cells[J]. Oncol Rep,2017,38(5):2951-2958.
[9] Zhu F,Li C,Jin XP,et al. Celastrol may have an anti-atherosclerosis effect in a rabbit experimental carotid atherosclerosis model[J].Int J Clin Exp Med,2014,7(7):1684-1691.
[10] Ross R. Atherosclerosis—an inflammatory disease[J]. N Engl J Med,1999,340(2):115-126.
[11]刘俊田.动脉粥样硬化发病的炎症机制的研究进展[J].西安交通大学学报(医学版),2015,36(2):141-152.
[12] Zhang B,Wu T,Chen M,et al. The CD40/CD40L system:A new therapeutic target for disease[J]. Immunol Lett,2013,153(1/2):58-61.
[13]薛凌,邱雅慧,张扬,等. CD40-CD40配体系统对兔动脉粥样硬化形成的影响[J].现代预防医学,2012,39(13):3318-3321.
[14] Lutgens E,Cleutjens KB,Heeneman S,et al. Both early and delayed anti-CD40L antibody treatment induces a stable plaque phenotype[J]. Proc Natl Acad Sci U S A,2000,97(13):7464-7469.
[15]程军,李金平,田卓,等.南蛇藤素对ApoE基因敲除小鼠主动脉粥样硬化斑块内CD40配体表达、巨噬细胞和平滑肌细胞数量的影响[J].中国病理生理杂志,2009,25(3):601-603.
[16] Thiele JR,Zeller J,Bannasch H,et al. Targeting C-reactive protein in inflammatory disease by preventing conformational changes[J]. Mediators Inflamm,2015,2015:372432.
[17] Stancel N,Chen CC,Ke LY,et al. Interplay between CRP,Atherogenic LDL,and LOX-1 and its potential role in the pathogenesis of atherosclerosis[J]. Clin Chem,2016,62(2):320-327.
[18] Pasceri V,Willerson JT,Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells[J]. Circulation,2000,102(18):2165-2168.
[19]徐艳杰,程晓曙. C反应蛋白与动脉粥样硬化[J].生命科学,2012,24(5):450-455.
[20]程军,李金平,田卓,等.南蛇藤素对载脂蛋白E基因敲除小鼠主动脉壁C反应蛋白及组织因子表达的影响[J].中国动脉硬化杂志,2008,16(5):341-344.
[21] Gong Z,Xing S,Zheng F,et al. Increased expression of macrophage migration inhibitory factor in aorta of patients with coronary atherosclerosis[J]. J Cardiovasc Surg(Torino),2015,56(4):631-637.
[22]储莉,刘伏元,王烈成.巨噬细胞移动抑制因子与动脉粥样硬化的相关性[J].广东医学,2015,36(5):680-682.
[23]徐斌,尹彤,赵玉生.巨噬细胞移动抑制因子在动脉粥样硬化中的作用研究进展[J].中国动脉硬化杂志,2004,12(2):238-240.
[24]杨瑞芳,阴彦龙,杨敏清,等.基质金属蛋白酶与动脉粥样硬化及斑块破裂的关系[J].分子影像学杂志,2017,40(4):482-485.
[25] Deleon-Pennell KY,Altara R,Yabluchanskiy A,et al. The circular relationship between matrix metalloproteinase-9 and inflammation following myocardial infarction[J]. IUBMB Life,2015,67(8):611-618.
[26] Kurzepa J,Madro A,Czechowska G,et al. Role of MMP-2 and MMP-9 and their natural inhibitors in liver fibrosis,chronic pancreatitis and non-specific inflammatory bowel diseases[J]. Hepatobiliary Pancreat Dis Int,2014,13(6):570-579.
[27] Galis ZS,Sukhova GK,Lark MW,et al. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques[J]. J Clin Invest,1994,94(6):2493-2503.
[28]李金平,程军,田卓,等.南蛇藤素对ApoE基因敲除小鼠主动脉壁MIF及MMP-9表达的影响[J].第三军医大学学报,2008,30(9):827-830.
[29]欧思琳,李茹冰. NF-κB在动脉粥样硬化疾病中的研究进展[J].中国免疫学杂志,2018,34(7):1095-1101.
[30] Lenardo MJ,Baltimore D. NF-kappa B:A pleiotropic mediator of inducible and tissue-specific gene control[J]. Cell,1989,58(2):227-229.
[31] Wang Y,Wang X,Sun M,et al. NF-κB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell[J]. Biochem Biophys Res Commun,2011,411(3):543-548.
[32] Pateras I,Giaginis C,Tsigris C,et al. NF-κB signaling at the crossroads of inflammation and atherogenesis:Searching for new therapeutic links[J]. Expert Opin Ther Targets,2014,18(9):1089-1101.
[33] Li Q,Syrovets T,Simmet T,et al. Plasmin induces intercellular adhesion molecule 1 expression in human endothelial cells via nuclear factor-κB/mitogen-activated protein kinases-dependent pathways[J]. Exp Biol Med(Maywood),2013,238(2):176-186.
[34] Gu L,Bai WL,Li S,et al. Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress[J]. PLo S One,2013,8(6):e65477.
[35]赖平.脂质在动脉粥样硬化早期病理变化过程中作用的研究进展[J].赣南医学院学报,2017,37(6):995-1000.
[36] Gluba-Brzózka A,Franczyk B,Banach M,et al. Do HDL and LDL subfractions play a role in atherosclerosis in end-stage renal disease(ESRD)patients?[J]. Int Urol Nephrol,2017,49(1):155-164.
[37] Bandeali S,Farmer J. High-density lipop-rotein and atherosclerosis:The role of antioxidant activity[J]. Curr Atheroscler Rep,2012,14(2):101-107.
[38]张颖.南蛇藤生物活性成分分析及其抗动脉粥样硬化药效评价[D].济南:山东农业大学,2013.
[39] Sawamura T,Kume N,Aoyama T,et al. An endothelial receptor for oxidized low-density lipoprotein[J]. Nature,1997,386(6620):73-77.
[40]郑旭,张梦诃,邓姣,等. LOX-1在动脉粥样硬化中的作用研究新进展[J].心脏杂志,2018,30(2):212-217.
[41] Kataoka H,Kume N,Miyamoto S,et al. Expression of lectinlike oxidized low-density lipoprotein receptor-1 in human atherosclerotic lesions[J]. Circulation,1999,99(24):3110-3117.
[42] Li DY,Chen HJ,Mehta JL. Statins inhibit oxidized-LDL-mediated LOX-1 expression,uptake of oxidized-LDL and reduction in PKB phosphorylation[J]. Cardiovasc Res,2001,52(1):130-135.
[43] Gimbrone MA Jr,García-Carde1a G. Endothelial cell dysfunction and the pathobiology of atherosclerosis[J]. Circ Res,2016,118(4):620-636.
[44]林艾雯,陈竹君.动脉粥样硬化与内皮细胞损伤机制的研究进展[J].岭南心血管病杂志,2015,21(4):580-582.
[45] Asahara T,Murohara T,Sullivan A,et al. Isolation of putative progenitor endothelial cells for angiogenesis[J]. Science,1997,275(5302):964-967.
[46] Huang S,Tang Y,Cai X,et al. Celastrol inhibits vasculogenesis by suppressing the VEGF-induced functional activity of bone marrow-derived endothelial progenitor cells[J]. Biochem Biophys Res Commun,2012,423(3):467-472.
[47] Lu C,Yu X,Zuo K,et al. Tripterine treatment improves endothelial progenitor cell function via integrin-linked kinase[J]. Cell Physiol Biochem,2015,37(3):1089-1103.
[48]张世田,唐汉庆,黄岑汉,等.氧化应激、炎症与冠状动脉粥样硬化关系的研究进展[J].右江医学,2017,45(2):235-239.
[49] Chen K,Keaney JF Jr. Evolving concepts of oxidative stress and reactive oxygen species in cardiovascular disease[J]. Curr Atheroscler Rep,2012,14(5):476-483.
[50] Zhu H,Jin X,Zhao J,et al. Probucol protects against atherosclerosis through lipid-lowering and suppressing immune maturation of CD11c+dendritic cells in STZ-induced diabetic LDLR-/-mice[J].J Cardiovasc Pharmacol,2015,65(6):620-627.
[51] Suzuki-Inoue K. Activation and inhibitory mechanisms of blood platelets[J]. Nihon Rinsho,2014,72(7):1212-1217.
[52] Franco AT,Corken A,Ware J. Platelets at the interface of thrombosis,inflammation,and cancer[J]. Blood,2015,126(5):582-588.
[53] Duchene J,von Hundelshausen P. Platelet-derived chemokines in atherosclerosis[J]. Hamostaseologie,2015,35(2):137-141.
[54]李金平.南蛇藤素对血小板功能及Apo E-/-小鼠动脉壁MIF、MMP-9表达的影响[D].重庆:第三军医大学,2008.