运用清热解毒法治疗慢性炎症相关病变的研究
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摘要
研究目的
本研究理论部分目的在于探讨内生热毒与慢性炎症的相关性,提出慢性炎症相关病变从热毒论治的思路;总结运用清热解毒法治疗慢性炎症相关病变的治疗规律,为临床辨证治疗此类疾病提供理论基础。实验部分以慢性炎症相关病变之一血管生成为靶点,研究清热解毒代表中药黄芩主要成分黄芩苷、金银花主要成分绿原酸对这一事件的影响作用,从而为临床用药提供实验依据,为清热解毒法实质的阐释提供科学的支持。
研究方法
理论部分以文献研究为主,全面总结前人研究成果,深度挖掘中西医不同领域理论内在联系,归纳出病理共性和治疗规律。实验方案分为体内和体外两部分,体内部分以鸡胚绒毛尿囊膜(CAM)为模型,观察药物黄芩苷、绿原酸对血管新生的影响作用;体外实验主要通过观察黄芩苷、绿原酸对血管生成不同环节(血管内皮基底膜的降解、内皮细胞的增殖、迁移以及管腔形成过程)的影响作用,来评价药物是否具有抗血管生成的活性。具体方法为:对血管内皮细胞Ea.hy926进行常规培养,采用MTT法检测药物对细胞增殖的影响;划痕实验、Transwell实验观察药物对内皮细胞迁移的影响;人工基质胶法观察药物对内皮细胞管腔形成的影响:明胶酶谱法检测药物对内皮细胞分泌MMP9、MMP2活性的影响。实验数据采用SPSS统计软件进行处理。
研究结果
本研究理论上对慢性炎症的内涵进行了全面总结,追踪国内外最新研究情况,重点阐述了慢性炎症相关病变尤其是血管生成的相关背景;从内生热毒与慢性炎症相关病变的各自特点,展开对二者相关性的探讨,总结了内在联系和规律:并由此进一步论述了运用清热解毒法治疗慢性炎症相关病变的用药规律。
实验部分的总结如下:1、体内实验即CAM法发现,无论黄芩苷还是绿原酸,各个浓度对血管生成有一定的抑制作用,且黄芩苷(浓5度0.01、0.1、1mM的抑制率分别为53.33%、66.67%、73.33%)呈现浓度依赖性。2、MTT实验表明,黄芩苷可以抑制Ea.hy926的增殖,OD值与空白组比较有显著性差异(p＜0.01),各个浓度(1、0.1、0.01mM)下细胞存活率分别为49.976%、70.78%、71.01%;绿原酸高浓度(1 mM)能够抑制细胞增殖,OD值与空白组比较有显著性差异(p＜0.05),但是无浓度依赖性。3、对划痕实验中各组细胞迁移率的统计数据来看,以姜黄素作对比,黄芩苷各个浓度(1、0.1、0.01mM)迁移率分别为20.67%、8.67%、97.33%,呈现较为明显的抑制作用;绿原酸各个浓度(1、0.1、0.01mM)迁移率分别为60.67%、1.0067%、1.2467%,有一定的浓度依赖性。4、Transwell实验结果显示,黄芩苷组的迁移细胞分别为29±4、41.8±17.12、36.7342.8±6.98、76.6±7.74,与对照组相比,具有显著性差异(p＜0.01),绿原酸组的迁移细胞分别为11.8±3.03、26.8±5.68、85.6±13.24、99±7.88,与对照组相比,具有显著性差异(p＜0.01)。5、在内皮小管形成实验中,高浓度黄芩苷、绿原酸(1mM)对Ea.hy926形成的内皮小管具有抑制和断裂作用。6、明胶酶谱实验中,黄芩苷有效地抑制了Ea.hy926分泌的胶原酶MMP-9、MMP-2,从而抑制内皮细胞的迁移,其中以MMP-2的抑制作用最为显著,且呈现明显的浓度依赖性。绿原酸的高浓度(1mM)能明显减弱MMP9、2的负染条带,低浓度差异不明显。
Research purposes
The purpose of the theory part in this study is to investigate the relevance of chronic inflammation and the toxicity and heat.the chronic inflammatory disease-related drugs from the heat of the idea of governance;summary of the use of heat-clearing and detoxifying treatment of chronic inflammatory diseases related to the treatment of the law,for clinical differentiation therapy in this provide a theoretical basis for diseases.Experimental part of one of chronic inflammatory disease-related angiogenesis as a target to study the heat-clearing and detoxifying the representative major components of Chinese medicine baicalin baicalin,honeysuckle main component of chlorogenic acid on the impact of the incident,so as to provide clinical experimental basis for the clearing away heat and toxic method to provide a scientific explanation of real support.
Research Methods
Theoretical part of research-oriented literature,a comprehensive summary of the results of previous studies,the depth of excavation in the Western theory of internal relations in different fields,into a pathology and treatment of common law.Experimental program is divided into two parts,in vivo and in vitro,in vivo portion of chicken chorioallantoic membrane(CAM) as a model to observe the drug of baicalin,chlorogenic acid on the impact of the role of angiogenesis;vitro mainly through the observation of baicalin,chlorogenic acid on the different aspects of angiogenesis(vascular endothelial basement membrane degradation,endothelial cell proliferation,migration and lumen formation) effect,to evaluate whether a drug of anti-angiogenesis activity.Specific methods for:Ea.hy926 of vascular endothelial cells to conventional training,the use of MTT assay of drugs on cell proliferation;scratch experiments, Transwell experiments to observe the drug on endothelial cell migration;artificial plastic matrix observed drugs on endothelial cells lumen formation;gelatin zymography detection of drugs on endothelial cell secretion of MMP9,MMP2 activity.Experimental data using statistical software SPSS for processing.
The results
In this study,in theory,chronic inflammation of the connotation of a comprehensive summary of the latest follow-up study at home and abroad,focusing on the chronic inflammatory disease,especially related to angiogenesis in the background;from the inside heat-related toxicity and chronic inflammatory disease of the respective characteristics carried out on the relevance of the two,summed up the internal links and the law;and thus further discusses the use of heat-clearing and detoxifying treatment of chronic inflammatory disease of drug-related law.
Part of the experiment are summarized as follows:1,in vivo experiments found that the CAM method,regardless of baicalin or chlorogenic acid,various concentrations of a certain degree of angiogenesis inhibition,and baicalin(0.01,0.1,1 mM concentration,respectively,the inhibitory rate for 53.33%,66.67%,73.33%) showed dose-dependent manner.2,MTT experiment showed that baicalin Ea.hy926 can inhibit the proliferation,OD values compared with the blank control group were significantly different(p＜0.01),various concentrations(1, 0.1,0.01 mM) under the cell survival rate was 49.976%,70.78%,71.01%;high concentration of chlorogenic acid(1 mM) could inhibit cell proliferation,OD values compared with the blank control group were significantly different(p＜0.05),but no dose-dependent manner.3, experiments on the scratch cell migration rate in each group statistical data,compared to curcumin,various concentrations of baicalin(1,0.1,0.01 mM) migration rates were 20.67%, 58.67%,97.33%,showed more obvious inhibition;various concentrations of chlorogenic acid (1,0.1,0.01 mM) migration rates were 60.67%,1.0067%,1.2467%,a certain degree of concentration-dependent.4,Transwell experiments showed that baicalin group migrated cells were 29±4,41.8±17.12,36.7342.8±6.98,76.6±7.74,compared with the control group with significant difference(p＜0.01),chlorogenic acid in cell migration group were 11.8±3.03,26.8±5.68,85.6±13.24,99±7.88,compared with the control group with significant difference (p＜0.01).5,in the endothelial tubule formation assay,the high concentration of baicalin, chlorogenic acid(1mM) on endothelial Ea.hy926 tubule formation and fracture with the role of inhibition.6,gelatin zymography experiments,Baicalin Ea.hy926 effectively inhibited the secretion of collagenase MMP-9,MMP-2,thereby inhibiting migration of endothelial cells, with inhibition of MMP-2 most significant,and a clear dose-dependent manner.Chlorogenic acid in high concentrations(1mM) significantly reduced MMP9,2 bands of negative staining, no obvious difference in low concentration.
本研究理论部分目的在于探讨内生热毒与慢性炎症的相关性,提出慢性炎症相关病变从热毒论治的思路;总结运用清热解毒法治疗慢性炎症相关病变的治疗规律,为临床辨证治疗此类疾病提供理论基础。实验部分以慢性炎症相关病变之一血管生成为靶点,研究清热解毒代表中药黄芩主要成分黄芩苷、金银花主要成分绿原酸对这一事件的影响作用,从而为临床用药提供实验依据,为清热解毒法实质的阐释提供科学的支持。
研究方法
理论部分以文献研究为主,全面总结前人研究成果,深度挖掘中西医不同领域理论内在联系,归纳出病理共性和治疗规律。实验方案分为体内和体外两部分,体内部分以鸡胚绒毛尿囊膜(CAM)为模型,观察药物黄芩苷、绿原酸对血管新生的影响作用;体外实验主要通过观察黄芩苷、绿原酸对血管生成不同环节(血管内皮基底膜的降解、内皮细胞的增殖、迁移以及管腔形成过程)的影响作用,来评价药物是否具有抗血管生成的活性。具体方法为:对血管内皮细胞Ea.hy926进行常规培养,采用MTT法检测药物对细胞增殖的影响;划痕实验、Transwell实验观察药物对内皮细胞迁移的影响;人工基质胶法观察药物对内皮细胞管腔形成的影响:明胶酶谱法检测药物对内皮细胞分泌MMP9、MMP2活性的影响。实验数据采用SPSS统计软件进行处理。
研究结果
本研究理论上对慢性炎症的内涵进行了全面总结,追踪国内外最新研究情况,重点阐述了慢性炎症相关病变尤其是血管生成的相关背景;从内生热毒与慢性炎症相关病变的各自特点,展开对二者相关性的探讨,总结了内在联系和规律:并由此进一步论述了运用清热解毒法治疗慢性炎症相关病变的用药规律。
实验部分的总结如下:1、体内实验即CAM法发现,无论黄芩苷还是绿原酸,各个浓度对血管生成有一定的抑制作用,且黄芩苷(浓5度0.01、0.1、1mM的抑制率分别为53.33%、66.67%、73.33%)呈现浓度依赖性。2、MTT实验表明,黄芩苷可以抑制Ea.hy926的增殖,OD值与空白组比较有显著性差异(p＜0.01),各个浓度(1、0.1、0.01mM)下细胞存活率分别为49.976%、70.78%、71.01%;绿原酸高浓度(1 mM)能够抑制细胞增殖,OD值与空白组比较有显著性差异(p＜0.05),但是无浓度依赖性。3、对划痕实验中各组细胞迁移率的统计数据来看,以姜黄素作对比,黄芩苷各个浓度(1、0.1、0.01mM)迁移率分别为20.67%、8.67%、97.33%,呈现较为明显的抑制作用;绿原酸各个浓度(1、0.1、0.01mM)迁移率分别为60.67%、1.0067%、1.2467%,有一定的浓度依赖性。4、Transwell实验结果显示,黄芩苷组的迁移细胞分别为29±4、41.8±17.12、36.7342.8±6.98、76.6±7.74,与对照组相比,具有显著性差异(p＜0.01),绿原酸组的迁移细胞分别为11.8±3.03、26.8±5.68、85.6±13.24、99±7.88,与对照组相比,具有显著性差异(p＜0.01)。5、在内皮小管形成实验中,高浓度黄芩苷、绿原酸(1mM)对Ea.hy926形成的内皮小管具有抑制和断裂作用。6、明胶酶谱实验中,黄芩苷有效地抑制了Ea.hy926分泌的胶原酶MMP-9、MMP-2,从而抑制内皮细胞的迁移,其中以MMP-2的抑制作用最为显著,且呈现明显的浓度依赖性。绿原酸的高浓度(1mM)能明显减弱MMP9、2的负染条带,低浓度差异不明显。
Research purposes
The purpose of the theory part in this study is to investigate the relevance of chronic inflammation and the toxicity and heat.the chronic inflammatory disease-related drugs from the heat of the idea of governance;summary of the use of heat-clearing and detoxifying treatment of chronic inflammatory diseases related to the treatment of the law,for clinical differentiation therapy in this provide a theoretical basis for diseases.Experimental part of one of chronic inflammatory disease-related angiogenesis as a target to study the heat-clearing and detoxifying the representative major components of Chinese medicine baicalin baicalin,honeysuckle main component of chlorogenic acid on the impact of the incident,so as to provide clinical experimental basis for the clearing away heat and toxic method to provide a scientific explanation of real support.
Research Methods
Theoretical part of research-oriented literature,a comprehensive summary of the results of previous studies,the depth of excavation in the Western theory of internal relations in different fields,into a pathology and treatment of common law.Experimental program is divided into two parts,in vivo and in vitro,in vivo portion of chicken chorioallantoic membrane(CAM) as a model to observe the drug of baicalin,chlorogenic acid on the impact of the role of angiogenesis;vitro mainly through the observation of baicalin,chlorogenic acid on the different aspects of angiogenesis(vascular endothelial basement membrane degradation,endothelial cell proliferation,migration and lumen formation) effect,to evaluate whether a drug of anti-angiogenesis activity.Specific methods for:Ea.hy926 of vascular endothelial cells to conventional training,the use of MTT assay of drugs on cell proliferation;scratch experiments, Transwell experiments to observe the drug on endothelial cell migration;artificial plastic matrix observed drugs on endothelial cells lumen formation;gelatin zymography detection of drugs on endothelial cell secretion of MMP9,MMP2 activity.Experimental data using statistical software SPSS for processing.
The results
In this study,in theory,chronic inflammation of the connotation of a comprehensive summary of the latest follow-up study at home and abroad,focusing on the chronic inflammatory disease,especially related to angiogenesis in the background;from the inside heat-related toxicity and chronic inflammatory disease of the respective characteristics carried out on the relevance of the two,summed up the internal links and the law;and thus further discusses the use of heat-clearing and detoxifying treatment of chronic inflammatory disease of drug-related law.
Part of the experiment are summarized as follows:1,in vivo experiments found that the CAM method,regardless of baicalin or chlorogenic acid,various concentrations of a certain degree of angiogenesis inhibition,and baicalin(0.01,0.1,1 mM concentration,respectively,the inhibitory rate for 53.33%,66.67%,73.33%) showed dose-dependent manner.2,MTT experiment showed that baicalin Ea.hy926 can inhibit the proliferation,OD values compared with the blank control group were significantly different(p＜0.01),various concentrations(1, 0.1,0.01 mM) under the cell survival rate was 49.976%,70.78%,71.01%;high concentration of chlorogenic acid(1 mM) could inhibit cell proliferation,OD values compared with the blank control group were significantly different(p＜0.05),but no dose-dependent manner.3, experiments on the scratch cell migration rate in each group statistical data,compared to curcumin,various concentrations of baicalin(1,0.1,0.01 mM) migration rates were 20.67%, 58.67%,97.33%,showed more obvious inhibition;various concentrations of chlorogenic acid (1,0.1,0.01 mM) migration rates were 60.67%,1.0067%,1.2467%,a certain degree of concentration-dependent.4,Transwell experiments showed that baicalin group migrated cells were 29±4,41.8±17.12,36.7342.8±6.98,76.6±7.74,compared with the control group with significant difference(p＜0.01),chlorogenic acid in cell migration group were 11.8±3.03,26.8±5.68,85.6±13.24,99±7.88,compared with the control group with significant difference (p＜0.01).5,in the endothelial tubule formation assay,the high concentration of baicalin, chlorogenic acid(1mM) on endothelial Ea.hy926 tubule formation and fracture with the role of inhibition.6,gelatin zymography experiments,Baicalin Ea.hy926 effectively inhibited the secretion of collagenase MMP-9,MMP-2,thereby inhibiting migration of endothelial cells, with inhibition of MMP-2 most significant,and a clear dose-dependent manner.Chlorogenic acid in high concentrations(1mM) significantly reduced MMP9,2 bands of negative staining, no obvious difference in low concentration.
引文
[1]曹澜.全身健康从防范慢性炎症开始[J].中老年保健,2007,5:64
[2]彭杰青.[M]病理学.上海科学技术出版社,1992.
[3]Maeurer MJ,Trinder P,Hommel G,et al.[J].Infect Immun,2000,68(5):2962-2970.
[4]王九平,李新红,连建奇,等[J].细胞与分子免疫学杂志,2000,16:336-337.
[5]闫朝武.细胞因子与慢性炎症[J].国外医学免疫学分册,2002,25(2):98
[6]Onodera S,Tanji H,Suzuki K,et al.[J].Cytokine,1999,11:163-167.
[7]Scola MP,Imagawa T,Boivin GP et al.Expression of angiogenic factors in juvenile rheumatoid arthritis:Correlation with revascularization of human synovium engrafted into SCID mice[J].Arthritis Rheum,2001,44(14):794-801.
[8]Gracie JA,Forsey RJ,Chan WL,et al.[J].Clin Invest,1999,104:1393-1401
[9]Cao R,Farnebo J,Kurimoto M,et al.[J].FASEB J,1999,13:2195-2202.
[10]Sakai T,Kusugami K,ishimura H,et al.[J].Gastroenterology,1998,114:1237-1243.
[11]Prieto J,Lensmar C,Roquet A,et al.[J].Respir Med,2000,94(8):806-814.
[12]齐发莲,张劭夫,陈世敏,等[J]免疫学杂志,1998,14:109-110
[13]张劭夫,张明,徐德斌,等[J]中华结核和呼吸杂志,2000,23:113-114
[14]荣海钦.[J]代谢综合征还是慢性炎症综合征,实用糖尿病杂志,2006,3(1):3
[15]Ross R.Atherosclerosis-an inflammatory disease[J].EngMed,1999,340:115-126
[16]Libby P,RidkerPM,MaseriA.Inflammation and atherosclerosis[J].Circulation,2002,105:1135-1143.
[17]冯宗忱.动脉粥样硬化血管壁的慢性炎症[J].中华心血管病杂志,2005,33(5):393-394.
[18]Bergstrom J,Lindholm B,Jr Lacson E,et a.l What are the causes and consequences of the chronic inflammatory state in chronic dialysis patients[J].Sem in Dia,12000,13(3):163-175.
[19]林蓉,甘伟杰,等.药物治疗动脉粥样硬化新途径-抗炎作用[J].中国药理学通报,2004,20(5):499-502.
[20]Fruchart JC,Nierman M C,Stroes ES,et al.New risk factors for atherosclerosis and patient risk assessment[J].Circulation,2004,109(23 Suppl 1):S15.
[21]勾忠平,李秀钧.糖尿病属慢性炎症性疾病[J]实用糖尿病杂志,2006,3(1):5
[22]Zick Y.Uncoupling insulin signaling by serine/threonine phosphorylation:a molecular basis for insulin resistance.[J].Biochemical Society Transactions 2004,32(Pt5):812-816.
[23]Bautista LE,Vera LM,Arenas IA,et al.Independent association between inflammatory markers(C-reactive protein,interleukin-6,and TNF-alpha)and essential hypertension[J].HumHypertens,2005,19(2):149-154.
[24]Shacter E,Weitzmansa.Chronic inflammation and cancer[J].Oncology,2002,16:217-226.
[25]Alberto Mantovani.cancer Inflaming metastasis[J]Nature 2009,457:36
[26]Mantovani,A.,Allavena,P.,Sica,A.& Balkwiil,F.Nature 454,436-444(2008).
[27]Luo,J.L.et al.Nature 446,690-694(2007).
[28]Sangaletti,S.et al.Cancer Res.68,9050-9059(2008).
[29]Balkwill F.Tumor necrosis factor or tumor promoting factor?[J].Cytokine Growth Factor Rev,2002,13:135-141.
[30]IshiiKJ,AkiraS.Innate immune recognition of nucleic acids:beyond toll-like receptors.[J]Cancer,2005,117:517-523
[31]彭杰青.[M]病理学.上海科学技术出版社,1992.
[32]Bian,X.W.,Chen,J.H.,Jiang,x.F.,etal.Angiogenesis as an immunophamracologic target in inflammation and cancer[J].Immunpohmaraco,2004,4(12):1537-1547.
[33]Murdoch C,Muthana M,Lewis CE(2005) Hypoxia regulates macrophage functions in inflammation.[J]Immunol 175:6257-6263
[34]Carmeliet P,Jain RK(2000) Angiogenesis in cancer and other diseases.Nature 407:249-257
[35]Kreis T,Vale R(1999) Guidebook to the extracellular matrix,anchor,and adhesion proteins.Wiley,New York
[36]Johnson BA,Haines GK,Harlow LA et al(1993) Adhesion molecule expression in human synovial tissue.Arthritis Rheum 36:137-146
[37]Gong R,Rifai A,Dworkin LD(2006) Anti-inflammatory effect of hepatocyte growth factor in chronic kidney disease:targeting the inflamed vascular endothelium.J Am Soc Nephrol 17:2464-2473
[38]Karin M(2006) Nuclear factor-kappaB in cancer development and progression.Nature 441:431-436
[39]Fiedler U,Reiss Y,Scharpfenecker M et al(2006) Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation.Nat Med 12:235-239
[40]Ley K.Pathways and bottlenecks in the web of inflammatory adhesion molecules and chemoattractants.Immunol Res,(2001)24:87-95
[41]Carla Costa,Joan Incio,Raquel Soares.Angiogenesis and chronic inflammation:cause or consequence?[J]Angiogenesis(2007) 10:149-166
[42]Judah Folkman.Angiogenesis:an organizing principle for drug discovery?[J]Nature(2007)6:273-286
[43]Jozsef TIMAR,Balazs D(O|¨)ME,Karoly FAZEKAS.Angiogenesis-Dependent Diseases and Angiogenesis Therapy[J]Pathology Oncology Research.(2001) 7:85-94
[44]宣鸣,温玉明.血管内皮细胞生长因子与肿瘤[J].国外医学口腔医学分册,1998,25(2):99-102.
[45侔萍.NADPH氧化酶在H2O2双向调节血管生成中的重要作用以及天然抗氧化物马先篙贰G的抑制血管和肿瘤生成作用[D]兰州大学博士学位论文.2007:11
[46]GetherHP,FerraraN.The role of VEGF in normal and neoplastic hematopoiesis[J]Mol Med,2003,81:20-31.
[47]Corss,M.J.,Claesson-Welsh.FGF and VEGF function in angiogenesis:signaling pathwyas,biological responses and the therapeutic inhibition[J].Trends Pharmacol Sci,2001,22(4):201-207.
[48]Huang,Z.,Bao,S.D.Roles of main pro-and anti-angiogenic factors in tumor angiogenesis[J].World J Gastroenterol,2004,10(4):463-470.
[49]G.Klein,E.V.,M.W.fraaije,W.A.Kampsa,E.S.J.M.de Bont.The possible role of matrix metalloproteinase(MMP)-2 and MMP-9 in cancer,e.g.acute leukemia[J].Oncology/Hematology,2004,50:87-100.
[50]Oike,Y.,Yasunaga,K.,Suda,T.Angiopoietin-related/angiopoietin-like proteins regulate angiogenesis[J].Int J Hematol,2004,80(1):21-28.
[51]Jin,H.,Varner,J.Integrins:roles in cancer development and as treatment targets[J].Br J Cancer,2004,90(3):561-565.
[52]Ruhrbegr,C.Endogenous inhibitors of angiogenesis[J].Journal of Cell Science,2001,114:3215-3216.
[53]Chen YX,Nakashima Y,Tanaka K,et al.Immunohistochemical expression of vascular endothelial growth factor/vascular permeability factor in atherosclerotic intimals of huamn coronary arteries.ATVB,1999,19:131-139.
[54]O'Brien ER,Garvin MR,Dev R,et al,Angiogenesis in human coronary atherosclerotic plaques[J].Am J Pathol,1994,145:883-894.
[55]Jeziorska M,Woolley DE.Neovascularization in early atherosclerotic lesions of human carotid arteries:its potential contribution to plaque development[J].Hum Pathol,1999,30:919-925.
[56]O'Brien KD,McDonald TO,Chair A,et al.Neovascular expression of E-selectin,ICAM-1 and VCAM-1in human atherosclerosis and their relation to intimal leukocyte content[J].Circulation,1996,93:672-682.
[57]任海霞,肖诚,李梢,等.类风湿性关节炎中的血管生成相关因子研究进展[J].中国中医基础医学杂志,2007,13(4):315.
[58]Koch,A.E.Angiogenesis as a target in rheumatoid arthritis[J].Ann Rheum Dis,2003,62 Suppl 2:60-67.
[59]Gargiulo,P.,Giusti,C.,Pietrobono,D.,et al.Diabetes mellitus and retinopathy[J].Dig Liver Dis,2004,36 Suppl 1:S101-105.
[60]欧林德.论“毒”当作为中医独立病因之一[J].湖南中医学院学报,1987,7(3):6-8
[61]周仲瑛.“伏毒”新识[J].世界中医药,2007,3(2):71-76
[62]于智敏.中医学之“毒”概念的演变[J].中国中医基础医学杂志,2005:(12):1
[63]鲁明源.现代生活方式与人类体质演化[J].山东中医药大学学报,2002,26(1):48
[64]吴伟,彭锐.冠心病热毒病机的探讨[J].新中医,2007,39(6):3-6
[65]马廷行,唐晓勇,李春华.滋阴清热解毒法治疗肺癌的研究进展[J].山东中医杂志,2008,27(3):207-210
[66]周春友,石岩.中医学对代谢综合征的认识和治疗[J].吉林中医药,2008,28(2):90-91
[67]梁爱华,陈明伟.热毒与血栓性疾病的临床相关性分析与探讨[J].中国中药杂志,2008,33(4):476-479
[68]范砚超,张国平,唐明.从毒论治动脉粥样硬化初探[J].山东中医杂志,2004,23(5):261-263
[69]吕崇山,杨叔禹,李学军,等.代谢综合征从毒论治病机探析[J]光明中医,2007,22(10):13-15
[70]陈苍舒,雷励.冠心病炎症机理与热毒痰瘀相关性探讨[J].中国中医急症,2007,16(3):311-313
[71]陆付耳,王智明,郭爱群.糖尿病从“毒”论治探讨[J].中国中医基础医学杂志,2002,8(5):335
[72]晁梁.周仲瑛教授从“三热”论治糖尿病的学术思想研究.[D]南京中医药大学博士学位论文,2007
[73]姬素梅.从热毒论治类风湿性关节炎[J].医药论坛杂志,2005,26(9):70-72
[74]张金峰.凌昌全癌毒学说运用经验[J]中医杂志,2008,49(8):693-695
[75]窦彩萍.葛健文运用清热解毒法治疗类风湿性关节炎经验[J]甘肃中医学院学报,2008,25(4):1-4
[76]丁书文,李晓,李运伦.热毒学说在心系疾病中的构建与应用[J].山东中医药大学学报,2004,28(6):413-416
[77]玉山江.糖尿病从热毒论治探要.[J]新疆中医药,2000,18(4):7-9
[78]陆付耳,王智明,郭爱群.糖尿病从“毒”论治探讨[J].中国中医基础医学杂志,2002,8(5):15-17
[79]陆付耳,李鸣真,叶望云.清热解毒治法研究的思路与方法[J].中国中西医结合杂志,2004,12(24):1124-1125
[80]郑虎占.中药现代研究与应用[M].北京:学苑出版社.1997.1535.
[81]于新,杜志坚,陈悦娇,等.白花蛇舌草提取物抗氧化作用的研究[J].食品与发酵工业,2002,28(3):10-13.
[82]吴厚铭,黄胜余,劳霞飞,等.白花蛇舌草免疫多糖结构的研究[J].有机化学,1992,12:428-431.
[83]单保恩,张金艳,杜肖娜,等.白花蛇舌草的免疫学调节活性和抗肿瘤活性[J].中国中西医结合杂志,2001,21(5):370-374.
[84]孟玮,邱世翠,刘志强,等.白花蛇舌草对小鼠骨髓细胞增殖和IL2生成的影响[J].滨州医学院学报,2004,27(4):256-257.
[85]李瑞,赵浩如,林以宁.白花蛇舌草水溶性提取物的抗肿瘤作用和对化疗损伤的保护作用的研究[J].Journal of Chinese pharmacetical sciences(中国药学:英文版),2002,11(2):58.
[86]高冬,高永琳,白平,等.白花蛇舌草对宫颈癌细胞钙信号的影响[J].福建中医学院学报,2002,12(4):37-39.
[87]王刚,董玫,刘秀书,等.半枝莲醇提物抗肿瘤活性的研究.[J]现代中西医结合杂志,2004,13(9):1141-1142
[88]叶健,徐锡坤,周健伟.复方半枝莲体外抗癌作用机理的实验研究[J].江苏医药,1999,25(8):604
[89]侯远生,张旭梅.鱼腥草注射液与小鼠体内抗菌作用研究[J].中国中药杂志,1990,15(4):221-222.
[90]邵兰,于庆海,吴红艳,等,合成鱼腥草素对小鼠免疫功能的影内[J].沈阳药科大学学报,1999,16(3):209-211.
[91]曹郡双,秦荣和.鱼腥草的药理作用及临床应用[J].现代中西医结合杂志,2001,10(6):572.
[92]王祝举,赵玉英,等.夏枯草化学成分的研究[J].药学学报,1999,34(9):679-681.
[93]陈鼎祺.夏枯草治疗高血压及防治动脉粥样硬化[J].中医杂志,1999,40(8):453.
[94]梁兴伦.四安胶囊对高脂血症模型的效应研究[J].成都中医药大学学报,1998,21(3):39-41.
[95]刘保林,朱丹妮,王刚.夏枯草醇提物对小鼠血糖的影响[J].中国药科大学学报,1995,26(1):44-46.
[96] Lee H,Lin JY.Antimutagenic activity of extracts from anticancer drugs in Chinese medicine[J].MutatRes,1988,204(2):229.
[97] Horikawa K,Mohri T,Tanaka Y,et al. Moderate inhibition of mutagenicity and carcinogenicity of benzopyrene,1,6-dini- tropyrene and 3,9-dinitrofluoranthene by Chinese medicinal herbs[J].Mutagenesis, 1994,9(6):523.
[98] Xia W B, Xue Z; Li S,et al. Chemical constituents from tuber of Cremastra appendiculata [J].China J Chin Mater Med(中国中药杂志), 2005,30(23): 1827-1830.
[99] Joong S S, Jin HK, Jiyong L,et al. Anti-angiogenic activity of a homoisoflavanone from Cremastra appendiculata[J].Planta Med, 2004,70(2): 171-173.
[1]Carla Costa,Joao Incio,Raquel Soares.Angiogenesis and chronic inflammation:cause or consequence?[J]Angiogenesis(2007) 10:149-166
[2]纪相福,史道华.黄芩苷的心脑血管作用研究进展[J]海峡药学,2006,18(5):10-12
[3]林红.黄芩苷抗肿瘤作用及机制研究进展[J].新医学学刊,2008,5(3):354
[4]吴卫华,康桢,欧阳冬生,等.绿原酸的药理学研究进展[J]天然产物研究与开发,2006,18:691-694
[5]叶菁,陈培丰.中药及其提取物抑制肿瘤血管生成的研究进展[J]浙江中医药大学学报,2007,31(4):530-532
[6]钱晓萍,刘宝瑞.中药抗肿瘤血管生成分子机理研究进展[J]现代肿瘤医学,2007,15(6):878-880
[7]Mary Richardson.Observations on the Use of the Avian Chorioallantoic Membrane(CAM) Model in Investigations into Angiogenesis[J].Cardiovascular & Haematological Disorders,2003,3,155-185
[8]陆付耳,李鸣真,叶望云.清热解毒治法研究的思路与方法[J].中国中西医结合杂志,2004,12(24):1124-1125
[9]Judah Folkman.Angiogenesis:an organizing principle for drug discovery?[J]Nature (2007)6:273-286
[10]Kim J,Shim J,Lee S,etal.Microarray-based analysis of antiangiogenic activity of demethoxycurcum in on human umbilical vein endothelial cells:crucial involvement of the down-regulation of matrixmetalloproteinase[J].Cancer Res,2002,93(12):1378-1385.
[11]郑伟,杨向红,吴丽娜.姜黄素抗血管生成分子机制的探讨[J]中国肿瘤临床,2007,34(12):683-684
[12]杨明,侯敢,黄迪南.明胶酶与恶性肿瘤[J].现代肿瘤医学.2008,16(1):130-133
[13]Tatsuo Iijima,Yuko Minami,Naoko Nakamura,et al.MMP-2 activation and stepwise progression of pulmonary adenocarcinoma:hnalysis of MMP-2 and MMP-9 with gelatin zymography[J].Pathology International 2004;54:295-301
[2]彭杰青.[M]病理学.上海科学技术出版社,1992.
[3]Maeurer MJ,Trinder P,Hommel G,et al.[J].Infect Immun,2000,68(5):2962-2970.
[4]王九平,李新红,连建奇,等[J].细胞与分子免疫学杂志,2000,16:336-337.
[5]闫朝武.细胞因子与慢性炎症[J].国外医学免疫学分册,2002,25(2):98
[6]Onodera S,Tanji H,Suzuki K,et al.[J].Cytokine,1999,11:163-167.
[7]Scola MP,Imagawa T,Boivin GP et al.Expression of angiogenic factors in juvenile rheumatoid arthritis:Correlation with revascularization of human synovium engrafted into SCID mice[J].Arthritis Rheum,2001,44(14):794-801.
[8]Gracie JA,Forsey RJ,Chan WL,et al.[J].Clin Invest,1999,104:1393-1401
[9]Cao R,Farnebo J,Kurimoto M,et al.[J].FASEB J,1999,13:2195-2202.
[10]Sakai T,Kusugami K,ishimura H,et al.[J].Gastroenterology,1998,114:1237-1243.
[11]Prieto J,Lensmar C,Roquet A,et al.[J].Respir Med,2000,94(8):806-814.
[12]齐发莲,张劭夫,陈世敏,等[J]免疫学杂志,1998,14:109-110
[13]张劭夫,张明,徐德斌,等[J]中华结核和呼吸杂志,2000,23:113-114
[14]荣海钦.[J]代谢综合征还是慢性炎症综合征,实用糖尿病杂志,2006,3(1):3
[15]Ross R.Atherosclerosis-an inflammatory disease[J].EngMed,1999,340:115-126
[16]Libby P,RidkerPM,MaseriA.Inflammation and atherosclerosis[J].Circulation,2002,105:1135-1143.
[17]冯宗忱.动脉粥样硬化血管壁的慢性炎症[J].中华心血管病杂志,2005,33(5):393-394.
[18]Bergstrom J,Lindholm B,Jr Lacson E,et a.l What are the causes and consequences of the chronic inflammatory state in chronic dialysis patients[J].Sem in Dia,12000,13(3):163-175.
[19]林蓉,甘伟杰,等.药物治疗动脉粥样硬化新途径-抗炎作用[J].中国药理学通报,2004,20(5):499-502.
[20]Fruchart JC,Nierman M C,Stroes ES,et al.New risk factors for atherosclerosis and patient risk assessment[J].Circulation,2004,109(23 Suppl 1):S15.
[21]勾忠平,李秀钧.糖尿病属慢性炎症性疾病[J]实用糖尿病杂志,2006,3(1):5
[22]Zick Y.Uncoupling insulin signaling by serine/threonine phosphorylation:a molecular basis for insulin resistance.[J].Biochemical Society Transactions 2004,32(Pt5):812-816.
[23]Bautista LE,Vera LM,Arenas IA,et al.Independent association between inflammatory markers(C-reactive protein,interleukin-6,and TNF-alpha)and essential hypertension[J].HumHypertens,2005,19(2):149-154.
[24]Shacter E,Weitzmansa.Chronic inflammation and cancer[J].Oncology,2002,16:217-226.
[25]Alberto Mantovani.cancer Inflaming metastasis[J]Nature 2009,457:36
[26]Mantovani,A.,Allavena,P.,Sica,A.& Balkwiil,F.Nature 454,436-444(2008).
[27]Luo,J.L.et al.Nature 446,690-694(2007).
[28]Sangaletti,S.et al.Cancer Res.68,9050-9059(2008).
[29]Balkwill F.Tumor necrosis factor or tumor promoting factor?[J].Cytokine Growth Factor Rev,2002,13:135-141.
[30]IshiiKJ,AkiraS.Innate immune recognition of nucleic acids:beyond toll-like receptors.[J]Cancer,2005,117:517-523
[31]彭杰青.[M]病理学.上海科学技术出版社,1992.
[32]Bian,X.W.,Chen,J.H.,Jiang,x.F.,etal.Angiogenesis as an immunophamracologic target in inflammation and cancer[J].Immunpohmaraco,2004,4(12):1537-1547.
[33]Murdoch C,Muthana M,Lewis CE(2005) Hypoxia regulates macrophage functions in inflammation.[J]Immunol 175:6257-6263
[34]Carmeliet P,Jain RK(2000) Angiogenesis in cancer and other diseases.Nature 407:249-257
[35]Kreis T,Vale R(1999) Guidebook to the extracellular matrix,anchor,and adhesion proteins.Wiley,New York
[36]Johnson BA,Haines GK,Harlow LA et al(1993) Adhesion molecule expression in human synovial tissue.Arthritis Rheum 36:137-146
[37]Gong R,Rifai A,Dworkin LD(2006) Anti-inflammatory effect of hepatocyte growth factor in chronic kidney disease:targeting the inflamed vascular endothelium.J Am Soc Nephrol 17:2464-2473
[38]Karin M(2006) Nuclear factor-kappaB in cancer development and progression.Nature 441:431-436
[39]Fiedler U,Reiss Y,Scharpfenecker M et al(2006) Angiopoietin-2 sensitizes endothelial cells to TNF-alpha and has a crucial role in the induction of inflammation.Nat Med 12:235-239
[40]Ley K.Pathways and bottlenecks in the web of inflammatory adhesion molecules and chemoattractants.Immunol Res,(2001)24:87-95
[41]Carla Costa,Joan Incio,Raquel Soares.Angiogenesis and chronic inflammation:cause or consequence?[J]Angiogenesis(2007) 10:149-166
[42]Judah Folkman.Angiogenesis:an organizing principle for drug discovery?[J]Nature(2007)6:273-286
[43]Jozsef TIMAR,Balazs D(O|¨)ME,Karoly FAZEKAS.Angiogenesis-Dependent Diseases and Angiogenesis Therapy[J]Pathology Oncology Research.(2001) 7:85-94
[44]宣鸣,温玉明.血管内皮细胞生长因子与肿瘤[J].国外医学口腔医学分册,1998,25(2):99-102.
[45侔萍.NADPH氧化酶在H2O2双向调节血管生成中的重要作用以及天然抗氧化物马先篙贰G的抑制血管和肿瘤生成作用[D]兰州大学博士学位论文.2007:11
[46]GetherHP,FerraraN.The role of VEGF in normal and neoplastic hematopoiesis[J]Mol Med,2003,81:20-31.
[47]Corss,M.J.,Claesson-Welsh.FGF and VEGF function in angiogenesis:signaling pathwyas,biological responses and the therapeutic inhibition[J].Trends Pharmacol Sci,2001,22(4):201-207.
[48]Huang,Z.,Bao,S.D.Roles of main pro-and anti-angiogenic factors in tumor angiogenesis[J].World J Gastroenterol,2004,10(4):463-470.
[49]G.Klein,E.V.,M.W.fraaije,W.A.Kampsa,E.S.J.M.de Bont.The possible role of matrix metalloproteinase(MMP)-2 and MMP-9 in cancer,e.g.acute leukemia[J].Oncology/Hematology,2004,50:87-100.
[50]Oike,Y.,Yasunaga,K.,Suda,T.Angiopoietin-related/angiopoietin-like proteins regulate angiogenesis[J].Int J Hematol,2004,80(1):21-28.
[51]Jin,H.,Varner,J.Integrins:roles in cancer development and as treatment targets[J].Br J Cancer,2004,90(3):561-565.
[52]Ruhrbegr,C.Endogenous inhibitors of angiogenesis[J].Journal of Cell Science,2001,114:3215-3216.
[53]Chen YX,Nakashima Y,Tanaka K,et al.Immunohistochemical expression of vascular endothelial growth factor/vascular permeability factor in atherosclerotic intimals of huamn coronary arteries.ATVB,1999,19:131-139.
[54]O'Brien ER,Garvin MR,Dev R,et al,Angiogenesis in human coronary atherosclerotic plaques[J].Am J Pathol,1994,145:883-894.
[55]Jeziorska M,Woolley DE.Neovascularization in early atherosclerotic lesions of human carotid arteries:its potential contribution to plaque development[J].Hum Pathol,1999,30:919-925.
[56]O'Brien KD,McDonald TO,Chair A,et al.Neovascular expression of E-selectin,ICAM-1 and VCAM-1in human atherosclerosis and their relation to intimal leukocyte content[J].Circulation,1996,93:672-682.
[57]任海霞,肖诚,李梢,等.类风湿性关节炎中的血管生成相关因子研究进展[J].中国中医基础医学杂志,2007,13(4):315.
[58]Koch,A.E.Angiogenesis as a target in rheumatoid arthritis[J].Ann Rheum Dis,2003,62 Suppl 2:60-67.
[59]Gargiulo,P.,Giusti,C.,Pietrobono,D.,et al.Diabetes mellitus and retinopathy[J].Dig Liver Dis,2004,36 Suppl 1:S101-105.
[60]欧林德.论“毒”当作为中医独立病因之一[J].湖南中医学院学报,1987,7(3):6-8
[61]周仲瑛.“伏毒”新识[J].世界中医药,2007,3(2):71-76
[62]于智敏.中医学之“毒”概念的演变[J].中国中医基础医学杂志,2005:(12):1
[63]鲁明源.现代生活方式与人类体质演化[J].山东中医药大学学报,2002,26(1):48
[64]吴伟,彭锐.冠心病热毒病机的探讨[J].新中医,2007,39(6):3-6
[65]马廷行,唐晓勇,李春华.滋阴清热解毒法治疗肺癌的研究进展[J].山东中医杂志,2008,27(3):207-210
[66]周春友,石岩.中医学对代谢综合征的认识和治疗[J].吉林中医药,2008,28(2):90-91
[67]梁爱华,陈明伟.热毒与血栓性疾病的临床相关性分析与探讨[J].中国中药杂志,2008,33(4):476-479
[68]范砚超,张国平,唐明.从毒论治动脉粥样硬化初探[J].山东中医杂志,2004,23(5):261-263
[69]吕崇山,杨叔禹,李学军,等.代谢综合征从毒论治病机探析[J]光明中医,2007,22(10):13-15
[70]陈苍舒,雷励.冠心病炎症机理与热毒痰瘀相关性探讨[J].中国中医急症,2007,16(3):311-313
[71]陆付耳,王智明,郭爱群.糖尿病从“毒”论治探讨[J].中国中医基础医学杂志,2002,8(5):335
[72]晁梁.周仲瑛教授从“三热”论治糖尿病的学术思想研究.[D]南京中医药大学博士学位论文,2007
[73]姬素梅.从热毒论治类风湿性关节炎[J].医药论坛杂志,2005,26(9):70-72
[74]张金峰.凌昌全癌毒学说运用经验[J]中医杂志,2008,49(8):693-695
[75]窦彩萍.葛健文运用清热解毒法治疗类风湿性关节炎经验[J]甘肃中医学院学报,2008,25(4):1-4
[76]丁书文,李晓,李运伦.热毒学说在心系疾病中的构建与应用[J].山东中医药大学学报,2004,28(6):413-416
[77]玉山江.糖尿病从热毒论治探要.[J]新疆中医药,2000,18(4):7-9
[78]陆付耳,王智明,郭爱群.糖尿病从“毒”论治探讨[J].中国中医基础医学杂志,2002,8(5):15-17
[79]陆付耳,李鸣真,叶望云.清热解毒治法研究的思路与方法[J].中国中西医结合杂志,2004,12(24):1124-1125
[80]郑虎占.中药现代研究与应用[M].北京:学苑出版社.1997.1535.
[81]于新,杜志坚,陈悦娇,等.白花蛇舌草提取物抗氧化作用的研究[J].食品与发酵工业,2002,28(3):10-13.
[82]吴厚铭,黄胜余,劳霞飞,等.白花蛇舌草免疫多糖结构的研究[J].有机化学,1992,12:428-431.
[83]单保恩,张金艳,杜肖娜,等.白花蛇舌草的免疫学调节活性和抗肿瘤活性[J].中国中西医结合杂志,2001,21(5):370-374.
[84]孟玮,邱世翠,刘志强,等.白花蛇舌草对小鼠骨髓细胞增殖和IL2生成的影响[J].滨州医学院学报,2004,27(4):256-257.
[85]李瑞,赵浩如,林以宁.白花蛇舌草水溶性提取物的抗肿瘤作用和对化疗损伤的保护作用的研究[J].Journal of Chinese pharmacetical sciences(中国药学:英文版),2002,11(2):58.
[86]高冬,高永琳,白平,等.白花蛇舌草对宫颈癌细胞钙信号的影响[J].福建中医学院学报,2002,12(4):37-39.
[87]王刚,董玫,刘秀书,等.半枝莲醇提物抗肿瘤活性的研究.[J]现代中西医结合杂志,2004,13(9):1141-1142
[88]叶健,徐锡坤,周健伟.复方半枝莲体外抗癌作用机理的实验研究[J].江苏医药,1999,25(8):604
[89]侯远生,张旭梅.鱼腥草注射液与小鼠体内抗菌作用研究[J].中国中药杂志,1990,15(4):221-222.
[90]邵兰,于庆海,吴红艳,等,合成鱼腥草素对小鼠免疫功能的影内[J].沈阳药科大学学报,1999,16(3):209-211.
[91]曹郡双,秦荣和.鱼腥草的药理作用及临床应用[J].现代中西医结合杂志,2001,10(6):572.
[92]王祝举,赵玉英,等.夏枯草化学成分的研究[J].药学学报,1999,34(9):679-681.
[93]陈鼎祺.夏枯草治疗高血压及防治动脉粥样硬化[J].中医杂志,1999,40(8):453.
[94]梁兴伦.四安胶囊对高脂血症模型的效应研究[J].成都中医药大学学报,1998,21(3):39-41.
[95]刘保林,朱丹妮,王刚.夏枯草醇提物对小鼠血糖的影响[J].中国药科大学学报,1995,26(1):44-46.
[96] Lee H,Lin JY.Antimutagenic activity of extracts from anticancer drugs in Chinese medicine[J].MutatRes,1988,204(2):229.
[97] Horikawa K,Mohri T,Tanaka Y,et al. Moderate inhibition of mutagenicity and carcinogenicity of benzopyrene,1,6-dini- tropyrene and 3,9-dinitrofluoranthene by Chinese medicinal herbs[J].Mutagenesis, 1994,9(6):523.
[98] Xia W B, Xue Z; Li S,et al. Chemical constituents from tuber of Cremastra appendiculata [J].China J Chin Mater Med(中国中药杂志), 2005,30(23): 1827-1830.
[99] Joong S S, Jin HK, Jiyong L,et al. Anti-angiogenic activity of a homoisoflavanone from Cremastra appendiculata[J].Planta Med, 2004,70(2): 171-173.
[1]Carla Costa,Joao Incio,Raquel Soares.Angiogenesis and chronic inflammation:cause or consequence?[J]Angiogenesis(2007) 10:149-166
[2]纪相福,史道华.黄芩苷的心脑血管作用研究进展[J]海峡药学,2006,18(5):10-12
[3]林红.黄芩苷抗肿瘤作用及机制研究进展[J].新医学学刊,2008,5(3):354
[4]吴卫华,康桢,欧阳冬生,等.绿原酸的药理学研究进展[J]天然产物研究与开发,2006,18:691-694
[5]叶菁,陈培丰.中药及其提取物抑制肿瘤血管生成的研究进展[J]浙江中医药大学学报,2007,31(4):530-532
[6]钱晓萍,刘宝瑞.中药抗肿瘤血管生成分子机理研究进展[J]现代肿瘤医学,2007,15(6):878-880
[7]Mary Richardson.Observations on the Use of the Avian Chorioallantoic Membrane(CAM) Model in Investigations into Angiogenesis[J].Cardiovascular & Haematological Disorders,2003,3,155-185
[8]陆付耳,李鸣真,叶望云.清热解毒治法研究的思路与方法[J].中国中西医结合杂志,2004,12(24):1124-1125
[9]Judah Folkman.Angiogenesis:an organizing principle for drug discovery?[J]Nature (2007)6:273-286
[10]Kim J,Shim J,Lee S,etal.Microarray-based analysis of antiangiogenic activity of demethoxycurcum in on human umbilical vein endothelial cells:crucial involvement of the down-regulation of matrixmetalloproteinase[J].Cancer Res,2002,93(12):1378-1385.
[11]郑伟,杨向红,吴丽娜.姜黄素抗血管生成分子机制的探讨[J]中国肿瘤临床,2007,34(12):683-684
[12]杨明,侯敢,黄迪南.明胶酶与恶性肿瘤[J].现代肿瘤医学.2008,16(1):130-133
[13]Tatsuo Iijima,Yuko Minami,Naoko Nakamura,et al.MMP-2 activation and stepwise progression of pulmonary adenocarcinoma:hnalysis of MMP-2 and MMP-9 with gelatin zymography[J].Pathology International 2004;54:295-301