姜黄素对血管平滑肌细胞增殖抑制作用及机理探讨
摘要
实验目的：观察姜黄素对血管平滑肌细胞增殖的抑制作用;探讨其作用机理。
方法：(1)体内实验：将实验大鼠分为4组：假手术组(N组)、模型组(M组)、高剂量药物作用组(H组)、低剂量药物作用组(L组)。行P53,Fas组化检测;Bcl-2、Bax免疫印迹检测；TUNEL染色。结果用麦克奥迪图象分析系统分析,计算每张片子的平均光密度,药物用组分别与模型组进行比较,行单因素方差分析,计算P值。(2)体外实验：将VSMC随机分为五组,分别为空白组、模型组(AngⅡ10-7mol/L)和模型+姜黄素1、2、3组(姜黄素剂量为10、20、40、80μmol/L),各组VSMC用相应的细胞培养液孵育48小时,分别应用MTT检测生长率,用流式细胞术检测VSMC的细胞周期构成比,用TUNEL检测凋亡率。实验数据用平均数±标准差(X±S)表示,各组之间的数值比较采用样本均数方差分析进行统计学分析。
结果：(1)体内实验：高剂量药物作用组和假手术组Fas、P53的表达低于模型组,P<0.05;低剂量药物作用组与模型组相比无显著性差异,P>0.05。高、低剂量药物作用组和假手术组的Bcl-2和TUNEL的农达低于模型组,P<0.05。高、低剂量药物作用组和假手术组Bax表达高于模型组,P<0.05。(2)姜黄素作用后的VSMC较模型组的VSMC都有增殖减少,并与姜黄素的浓度呈反比；姜黄素作用后的VSMCG0/G1期构成比较模型组的VSMC升高,与姜黄素的浓度呈正比,S期、G2/M期构成比较模型组的VSMC降低,增殖指数下降,S期与姜黄素的浓度呈反比,G2/M期与姜黄素的浓度无相关；姜黄素作用后的VSMC较模型组的VSMC凋亡率增加,并与姜黄素的浓度呈正比。
结论：姜黄素能抑制体内与体外平滑肌细胞Fas、P53表达;影响Bcl-2、Bax基因表达,促进血管平滑肌细胞凋亡;达到制平滑肌细胞增殖的作用。
Objeetive:To explore the influence of CUR on vascular smooth muscle cell proliferation and its mechanism. Methods:(1)In vivo test: Wistar rats were divided into 4 groups:big dose drug group, small dose drug group, mode group, false operation group.P53, Fas were detected by histoehemistry and were detected in Bcl-2. Bax by West Blot and TUNEL tests in these paraffin slices.The average light density of every slice were detected by computer image analysis system. The results were analyzed by one-way analysis of variance.And then the results of every group were compared with those of mode group by using Dunnet-t test. (2) In vitro test:Divide VSMC into 5 groups at random.The groups are respectively named with control group,modal group(AngⅡ10-/mol/L),modal+ Curcumin groups,among the model+ Curcumin groups, Curcumin is divided to 10、20、40、80μmol/L different density. Every group is cultured 48 hours.To determine the cell proliferation by MTT,to detect the cell cycle by flow cytometry,to detect the apoptosis by TUNEL.The experimental data was denoted to mean±standard deviation(x±s),use analysis of variance to statistics analyze the numerus compare of each group.
Results:(1) In vivo test:The expression of P53 and Fas in slices of three groups are lower than the mode group.Compared with P53 and Fas results of mode group there is significant difference from the results of false operation group and big dose drug group P<0.05. Compared with P53 and Fas results of mode group there is not significant difference from the results of small dose drug group P>0.05.The expression of Bcl2 in slices of three groups are lower than the mode group.Compared with Bcl2 and TUNEL test results of mode group there is significant difference from the results of false operation group, small and big dose drug group P<0.05. The expression of Bax in slices of three groups are higher than the mode group.Compared with Bax results of mode group there is significant difference from the results of false operation group, small and big dose drug group P<0.05..(2)In vitro test:The VSMC proliferation rate after Curcumin is lower than that after AngⅡ. It shows inverse proportion to the density of Curcumin. Constituent ratio of VSMC G0/G1 cell cycle after Curcumin is higher thanthat after AngⅡ. It shows direct proportion to the density of hebesser. Constituent ratio of VSMC S cell cycle、G2/M cell cycle and proliferation index after Curcumin is lower than those after AngⅡ.The S cell cycle shows inverse proportion to the density of Curcumin,the G2/M cell cycle doesn't relate to the density of Curcumin.The VSMC apoptosis rate after Curcumin is higher than that after AngⅡ.It shows direct proportion to the density of Curcumin.
CONCLUSION The results show that Curcumin can markedly inhibit expression of P53, Fas in vascular smooth muscle cells, adjust expression of Bax,Bcl2 gene relating with VSMC apoptosis and pomote VSMC apoptosis. Curcumin can Inhibit VSMC Proliferation.
方法：(1)体内实验：将实验大鼠分为4组：假手术组(N组)、模型组(M组)、高剂量药物作用组(H组)、低剂量药物作用组(L组)。行P53,Fas组化检测;Bcl-2、Bax免疫印迹检测；TUNEL染色。结果用麦克奥迪图象分析系统分析,计算每张片子的平均光密度,药物用组分别与模型组进行比较,行单因素方差分析,计算P值。(2)体外实验：将VSMC随机分为五组,分别为空白组、模型组(AngⅡ10-7mol/L)和模型+姜黄素1、2、3组(姜黄素剂量为10、20、40、80μmol/L),各组VSMC用相应的细胞培养液孵育48小时,分别应用MTT检测生长率,用流式细胞术检测VSMC的细胞周期构成比,用TUNEL检测凋亡率。实验数据用平均数±标准差(X±S)表示,各组之间的数值比较采用样本均数方差分析进行统计学分析。
结果：(1)体内实验：高剂量药物作用组和假手术组Fas、P53的表达低于模型组,P<0.05;低剂量药物作用组与模型组相比无显著性差异,P>0.05。高、低剂量药物作用组和假手术组的Bcl-2和TUNEL的农达低于模型组,P<0.05。高、低剂量药物作用组和假手术组Bax表达高于模型组,P<0.05。(2)姜黄素作用后的VSMC较模型组的VSMC都有增殖减少,并与姜黄素的浓度呈反比；姜黄素作用后的VSMCG0/G1期构成比较模型组的VSMC升高,与姜黄素的浓度呈正比,S期、G2/M期构成比较模型组的VSMC降低,增殖指数下降,S期与姜黄素的浓度呈反比,G2/M期与姜黄素的浓度无相关；姜黄素作用后的VSMC较模型组的VSMC凋亡率增加,并与姜黄素的浓度呈正比。
结论：姜黄素能抑制体内与体外平滑肌细胞Fas、P53表达;影响Bcl-2、Bax基因表达,促进血管平滑肌细胞凋亡;达到制平滑肌细胞增殖的作用。
Objeetive:To explore the influence of CUR on vascular smooth muscle cell proliferation and its mechanism. Methods:(1)In vivo test: Wistar rats were divided into 4 groups:big dose drug group, small dose drug group, mode group, false operation group.P53, Fas were detected by histoehemistry and were detected in Bcl-2. Bax by West Blot and TUNEL tests in these paraffin slices.The average light density of every slice were detected by computer image analysis system. The results were analyzed by one-way analysis of variance.And then the results of every group were compared with those of mode group by using Dunnet-t test. (2) In vitro test:Divide VSMC into 5 groups at random.The groups are respectively named with control group,modal group(AngⅡ10-/mol/L),modal+ Curcumin groups,among the model+ Curcumin groups, Curcumin is divided to 10、20、40、80μmol/L different density. Every group is cultured 48 hours.To determine the cell proliferation by MTT,to detect the cell cycle by flow cytometry,to detect the apoptosis by TUNEL.The experimental data was denoted to mean±standard deviation(x±s),use analysis of variance to statistics analyze the numerus compare of each group.
Results:(1) In vivo test:The expression of P53 and Fas in slices of three groups are lower than the mode group.Compared with P53 and Fas results of mode group there is significant difference from the results of false operation group and big dose drug group P<0.05. Compared with P53 and Fas results of mode group there is not significant difference from the results of small dose drug group P>0.05.The expression of Bcl2 in slices of three groups are lower than the mode group.Compared with Bcl2 and TUNEL test results of mode group there is significant difference from the results of false operation group, small and big dose drug group P<0.05. The expression of Bax in slices of three groups are higher than the mode group.Compared with Bax results of mode group there is significant difference from the results of false operation group, small and big dose drug group P<0.05..(2)In vitro test:The VSMC proliferation rate after Curcumin is lower than that after AngⅡ. It shows inverse proportion to the density of Curcumin. Constituent ratio of VSMC G0/G1 cell cycle after Curcumin is higher thanthat after AngⅡ. It shows direct proportion to the density of hebesser. Constituent ratio of VSMC S cell cycle、G2/M cell cycle and proliferation index after Curcumin is lower than those after AngⅡ.The S cell cycle shows inverse proportion to the density of Curcumin,the G2/M cell cycle doesn't relate to the density of Curcumin.The VSMC apoptosis rate after Curcumin is higher than that after AngⅡ.It shows direct proportion to the density of Curcumin.
CONCLUSION The results show that Curcumin can markedly inhibit expression of P53, Fas in vascular smooth muscle cells, adjust expression of Bax,Bcl2 gene relating with VSMC apoptosis and pomote VSMC apoptosis. Curcumin can Inhibit VSMC Proliferation.
引文
[1]Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.J Immunol Methods.1983:65:55-63
[2]Molinari BL, Tasat DR, Palmieri MA, O Connor SE, Cabrini RL. Cell-based quantitative evaluation of the MTT assay. Anal Quant Cytol Histol. 2003:25:254-62
[3]Bruggisser R, von Daeniken K, Jundt G, et al. Interference of plant extraets phytoestrogens and antjoxidants with the MTT tetrazolium assay. Planta Med.2002:68:445-8
[4]Chen Y. Yang L, Lee TJ.Oroxylin A inhibition of lipopolysaceharide-ndueed iNOS and COX-2 gene expression via suppression of nuclear factor-kappaB activation. Biochem Pharmacol 2000:59:1445-57:
[5]Chen YC,Shen SC,Lee WR, et al. Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of Caspase3 Caseade but independent of reactive oxygen species production. Biochem Pharmacol2002;64:1713-24;
[1]Yao C,Wu Z, Wu Y. The changing pattern of cardiovascular disease inChina. World Health Stat Q.1993:46(2):113-8
[2]Brophy JM, Belisle P, Joseph L.Evidence for use of coronary stents. A hierarchical Bayesian meta-analysis. Ann Intern Med 2003;138(10):777-86.
[3]Park SW, Lee CW, Hong MK, Kim JJ, Cho GY, Nah DY,Park SJ.. Randomized comparison of coronary stenting with optimal balloon angioplasty for treatment of lesions in small coronary arteries.Eur Heart J,2000:21 (12):1785-9.
[4]Sanchez PL, Rodriguez-AlemParte M, Colon-Hernandez PJ, et al. Directional coronary atherectomy vs rotational atherectomy for the treatment of in-stent restenosis of native coronary arteries.Catheter Cardiovasc Interv. 2003:58:155-61.
[5]Nakatani M, Takeyama Y, Shibata M, et al. Mechanisms of restenosis after coronary intervention:difference between plain old balloon angioplasty and stenting. Cardiovasc Pathol.2003; 12:40-8
[6]Fattori R, Piva T. Drug-eluting stents invascular intervention. Lancet.2003; 361(9353):2470-9
[7]Hanke H, Strohschneider T, Obethoff M, Betz E, Karsch KP. Time course of smooth muscle cell proliferation in the intima and media of arteries following experiment alangioplasty.CircRes.1990:67(3):651-9
[8]Bennett MR, O Sullivan M. Mechanisms of angioplasty and sten restenosis: implications for design of rational therapy.Pharmacol Ther 2001;91(2):149-66
[9]Wang Z, Hsieh TC, Zhang Z, Ma Y, WU JM. Identification and purification of resveratrol targeting proteins using immobilized resveratrol affinity chomatography. Bio Chemical and biophysical research communications. 2004:323(3):743-749.
[10]Sun K, Al-Regaiey M. Mastemak B, et al. Local expression of GH and IGF-1 in the hippocampus of GH-deficient long-lived mice. Neuro biology of Aging, 26(6)929-937.
[11]Shimizu M, Deguehi A, Hara Y, et al. EGCG inhibits activation of the insulin-like growth factor-1 receptor in human colon cancer cells. Biochem Biophys Res Commun 2005:334:947-953.
[12]Hehtert JM, Dupuy E, Laplace MC, et al. Thrombin induce endothelial cell growth via both a proteolytic and a non-proteolytic pathway. Biochem J,1994:303(ptl):227-231.
[13]Yohsida Y, Mitsumata M, Yamane T. Moprhology and increase growth rate of atherosclerotic intimal smooth-muscle cells. Arch Pathol Lab Med,1988, 112:987-996.
[14]Vu TK, Hunag DT, Wheatno VI, et al. Molecular cloning of a functional thrombni recpetor reveals a novel proteolytic mechanism of recpetor activition.Cell,1991:64(6):1057-068.
[15]McNamara CA, Sarembock JJ, Gmple IW, et al. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated recpetor. J Clin Invest,1993:91 (1):94-98.
[16]王启贤,吕俊升.凝血.酶对大鼠血管平滑肌细胞血小板源性生长因子基因表达的影响.¨中国动脉硬化杂志,2000,8(：)126-31.
[17]Steffen Bassus, Olaf Herkert, Nicola Kronemann. Thrombin causes vascular endothelial growth factor expression in vascular smooth muscle cells.Arterioscler thromb vase Biol,2001,21 (9):1550-1555.
[18]Walton SP, Stephanopoulos GN, Yarmush ML, et al. Thermodynamic nand kinetic-characterization of oligodexynucleotide binding to a structured mRNA. J Bio Phys,2002,82(1):366-377
[19]Seiler SM. Thombin receptor antagonists. Semin thromb Hemost 1996:22(3):223-232.
[20]Bennett MD, Evan GI, Schwarz SM. Apoptosis of rat vascular smooth muscle cells is regulated by p53-dependent and -independent pahtways. Cicr Res, 1995,77:266
[21]Inagaki Y, Yamagishi S, Amano S, et al. Interferon gamma induced apoptosis and activation of THP-1 macrophages. Life Sci.2002 Oct 11;71(21):2499
[22]Miyashita T, Reed JC.Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell,1995 Jan 27;80(2):293
[23]姜泊.细胞凋亡基础与临床.北京：人民军医出版社,1997.167
[24]Matsusaka T.Ichikawa I.Biological functions of angiotensin and its receptors. Annual Review of Physiology,1997.59:395-412.
[25]Hanada M.Saito E.Kambe T,et al.Evidence for the involvement of platelet-derived growth facto in the angiotensin-induced growth of rat vascularsmooth muscle cells.Biol Pharm Bull,1999.22(2):137-141.
[26]Mondrof UF,Geiger H,Herrero M.et al.Involvement of the platelet-derived growth factor receptor in angiotensin-induced activation of extracellular regulated dinases 1 and 2 in human mesangial cells.FEBS Lett.2000. 72(1):129-132.
[27]Touyz RM,HeqDeng LY,Schiffrin EL.Role of extracellular signal-regulated kinases in angiotensin Ⅱ-stimulated contraction of smooth muscle cells from human resistance vessels.Circulation.1999.99:392-399.
[28]Touyz RM,He El Mabrouk M.et al.Diferential activation of ERK1/2 and p38MAP kinase by angiotensin II type I receptor in vascular smooth muscle cells from WKY and SHR.Journal of Hypertension.2001.19:553-559.
[29]Touyz RM,Wu XH.Heq,et al.Role of c-Src in the regulation of vascular contraction and Ca2+ signaling by angiotensin II in human vascular smooth muscle cells.Journal of Hypertension.2001.19:441-449.
[30]Hsueh WA.Do YS.Anderson PW,et al.Angiotensin H in cell growth and matrix production.Advances in Experimental Medicine and Biology,1995.377:217-223.
[31]Thomas SM.Brugge JS.Cellular functions regulated by Src family kinases. Annual Review of Cell Division.1997.13:513-609.
[32]Ihle JN.Cytokine receptor signaling.Nature.1995.377:591-594.
[33]Fabio Rossi.Cora Bertone.Silvia Pctricca,et al.Adrenomedullin antagonizes angiotensin Ⅱ-stimulated proliferation of human aortic smooth muscle cells. Peptides,2006,(27):2935-2941.
[34]张玉珍.高平进.王兴宇,等.血管紧张素Ⅱ对血管平滑肌细胞增殖的影响.中国病理生理杂志,2000.16(10)：1007.
[35]Anger M.Lompm AM.Valot O.et al.Cellular distribution of Ca2+ release channels in rat cardiac hypertrophy induced aortic stenosis.Circulation. 1998:98(22):2477-2486
[36]Lee HW.Eghbali WM.Estrogen enhances proliferative capacity of cardiac fibroblasts by estrog receptor-and mitogen-activated protein kinase-dependent pathways.J Mol Cell Cardiol.1998.30(11):1359-368
[37]Rabikin SW.Sunga PS.Sanghera JS.et al.Reduction of angiotensin Ⅱ-induced activation of mitogen-activated ptotein kinase in cardiac hypertrophy[J].Cell Mol Life Sci.1997:53(11):955-959
[38]Pinton P.Ferrari D,Papizzi Z,et al.The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis:significance for the molecular mechanism of Bcl-2 action.EMBO J.2001:20:2690-2701.
[1]Detre K, Holubkov R, Kelsey S, et al. Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981.The National Heart, Lung and Blood Institute Registry. N Engl J Med 1988:318:265-270.
[2]Kurbaan AS, Bowker TJ, Iisley CD, Riekards AF. Impact of postangioplasty restenosis on comparisons of outcome between angioplasty and bypass grafting. Coronary AngioPlasty versus Bypass Revascularisation Investigation (CABRI) Investigators.Am J Cardiol.1998:82:272-6
[3]Serruys PW, Unger F, Van Hout BA, et al. The ARTS study(Arterial Revaseularization Therapies Study). SeminInteryCardiol.1999:4:209-19
[4]Fischman DL. L eon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Resteno sis Study Investigators. N Engl J M ed.1994,331 (8):496-501.
[5]Elezi S. Kastrat iA.N eumann FJ. et al. Vessel size and longterm outcome after coronary stent placement.Circulat ion,1998:98:1875-1880.
[6]Chervu A, Moore WS. An overview of intimal hyperplasia. Surg Gynecol Obstet.1990:171:433-7.
[7]Heekenkam PJ, Gawenda M, Brunkwall J. Vascular restenosis. Basic Science and clinical implications. J Cardiovase Surg(Torino).2002;43:349-57
[8]Surh YJ. Anti-tumor promoting potenial of selected spice ingredients with antioxidative and anti-inflammatory activities:a short review. Food Chem Toxicol,2002,4(8):1091
[9]Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin:preclinical and clinical studies.AnticancerRes,2003,23(1A):363
[10]李冬保.动脉粥样硬化和在狭窄中平滑肌细胞的凋亡与增殖.国外医老年医学分册,2000;32(1)8
[11]M.R.Benett, GI Even. Apoptosis of rats smooth muscle cell is regulated by P53 dependent and independent Pathway. Imperial cancer research,2000:12(4)45 sehisandrinBandemodin.PlantaMed2002:68:951-6
[12]12 Vousden KH. Activation of the P53 tumor suppressor Protein. Biochimica Bio Physica Acta2002; 1602:47-59
[13]Sharpless NE.Depinho RA. P53:good cop/bad cop.Cell2002:110:9-12
[14]Yang J, Duerksen- Hughes P. A new approach to identifying genotoxic carcinogens:P53 induction as an indicator of genotoxic damage. Carcinogenesis.1998:19:1117-1125
[15]SattlerM.Liang H.Nettesheim D.et al.Structure of Bcl-XL-Bax Peptide Complex:Recognition between regulators of apop tosis.Science.1997.275(5302):983
[16]Tsujimoto Y.Croce CM.Analysis of the structure.transcrip ts.and protein product of bcl-2.the gene involved in human follicular lym2 phoma.PN AS.1986.83(14):5214-5218
[17]王祥贵,冯义柏.朱利民,等.同型半胱氨酸对人血管平滑肌细胞凋亡及bax、bcl-2表达的影响中国全科医学2005年3月第8卷第6期743
[1]Huast DA, More RH, Movat HZ. The role of smooth muscle cells in the fibrogenesis of atherosclerosis. American journal pathology,1960,37:377-387.
[2]Schwartz SM, CamPbell GR, Campbell JH. Replication of smooth muscle cells in vascular disease. Circulation Research,1986,58:427-444.
[3]Murrya TR, Marshall BE, Macarak EJ. Constraction of vascular smooth muscle in cell culutre. Journal cell physiology,1990,143:26-38.
[4]韩启德,文允锐.血管生物学.北京：1997,北京医科大学、中国协和医科大学联合出版社.
[5]Hehtert JM, Dupuy E, Lpalace MC, et al. Thrombin induce endohthelial cell growth via both a proteolytic and a non- proteolytic pathway. Biochme J, 1994;303(ptl):227-231
[6]Yohsida Y, Mitsmuata M, Yamane T. Moprhology and increase growth rate of atherosclerotic intimal smooth-muscle cells. Arch Pathol Lab Med,1988, 112:987-996
[7]Vu TK, Huang DT, Wheaton VI, et al. Molecular cloning of a fuctional thrombin recpetor reveals a novel proteolytic mechanism of recpetor activition.Cell,1991;64(6):1057-068
[8]McNamara CA, Sarembock U, Gmple IW, et al. Thrombin stimulates proliefartion of cultured rat aortic smooth muscle cells by a porteolytically activated recptor.J Clin Invest,1993:91(1):94-98
[9]工启贤,吕俊升.凝血酶对大鼠血管平滑肌细胞血小板源性生长因子基因表达的影响.中国动脉硬化杂志,2000,8(1)：26-31
[10]Steffen Bassus, Olaf Herkert, Nicola Kronmeann. Thrombin causes vascular endothelial growth factor expression invascular smooth muscle cells. Arterioscler thromb vasc Biol,2001,21(9):1550-1555
[11]Walton SP, Stephanopoulos GN, Yarmush ML, et al. Thermodynamic and kinetic-characterization of oligo dexynucleotide binding to a structured mRNA. J Bio Phys,2002,82(1):366-377
[12]宪敏,米立国,赵秀文,等.反义TR和p21双基因共同表达对人主动脉平滑肌细胞增殖与凋亡的作用.中国医学科学院学报,2002；24(：4)339-342
[13]Bennett MD, Evan GI, Schwarz SM. Apoptosis of rat vascular smooth muscle cells is regulated by P53-dependent and-in dependent pahtways. Cicr Res, 1995,77:266
[14]Inagaki Y, Yamagishi S, Amano S, et al. Interferon gamma induced apoptosis and activation of THP-1 macrophages. Lifd Sci.2002 oct11;71(21):2499
[15]Miyashita T, Reed JC.Tumor supperssor P53 is a direct transcriptional activator of the human bax gene. Cell,1995 Jan27;80(2):293
[16]姜泊.细胞凋亡基础与临床.北京：人民军医出版社,1997.167
[17]李冬宝(综述),谢苗荣(审校).动脉粥样硬化与再狭窄中平滑肌细胞的调亡与增殖.2003；20(1)41
[18]Paula Bray, Alex Agrotis, Alex Bobik. Transforming Growth Factor-β and receptor Tyrosine Kinase-Activating Growth Factors Negatively Regulate Collagen Genes in Smooth muscle of Hypertensive Rats. Scienttific contribtion,1999
[19]Okura T, Lgasem, ETC. Platelet derived growth factor induces apoptpsis invascular smooth muscle cell:roles of the BCL-2 family. Circulation,2001
[20]朱中生(综述),王晋明(审校).高血压性动脉硬化的发生机制研究进展.岭南心血管杂志,2001；10(1)18
[21]Nikol S,Weir L,Sullivan A,et al.Persistently in creased expression of the transforing growth factor-beta Ⅰ gene in human vascular restenosis:Analysis of 62 patiants with one or mine episocles of restenosis.Cardiovasc Pathol 1994;3:57-64
[22]郭庆,温进坤.碱性纤维母细胞生长因子对血管平滑肌细胞增殖的影响.中国动脉硬化杂志,1996,4：168-171
[23]石缨,温进坤.新生小牛血清、碱性成纤维细胞生长因子和肝素对大鼠血管平滑肌细胞骨桥蛋白表达的影响.中国动脉硬化杂志,1996,7：1-3
[24]周秀霞,温进坤,韩梅.含活血化癖中药血清对血管平滑肌细胞迁移相关基因表达的影响.河北医科大学学报,2000,21：217
[25]石缨,温进坤.新生小牛血清、碱性成纤维细胞生长因了和肝素对大鼠血管平滑肌细胞迁移的影响.中国动脉硬化杂志,1998,6：189-192
[26]邢东琦,高广道.Ang的胞内信号转导径路[J].国外医学生理、病理科学与临床分册.1998；18(3)：233-236
[27]Xiao F, Puddefoot JR,Barker S,Mechanism for aldosterone potential-tionof angiotensin Ⅱ-stimulated rat arterial smooth muscle cell proliferation. Hypertension.2004;44:340-345.
[28]工启贤,吕俊升.凝血酶对大鼠血管平滑肌细胞血小板源性生长因子基因表达的影响.中国动脉硬化杂志,2000,8(：)126-31
[29]Steffen Bassus, Olaf HerkCrt, Nicola Kronmeann. Thrombin causes vascular endothelial growth factor expression in vascular smooth muscle cells.Arterioscler throm vasc Biol,2001,21(9):1550-1555
[30]任国峰,王宗立,李拥军,等.反义大鼠凝血酶受体基因的构建及其对主动脉血管平滑肌细胞增生的作用.基础医学与临床,2000；20(3)：47
[31]Nelken NA, Soifer SJ, O'keeef J,et al. Thrombin receptor expression in nomral and arterioscler human arteries. J Clin Ivest,1992;90(4):1614-1621
[32]Wilocx JN, Rodriguez J, Subramanian R, et al. Characterizaton of thrombin receptor expression furing. Circ Res,1994;75(6):1029-1038
[33]Pakala R, Liang CT, Benedict CR. A peptide analogue of thrombin receptor-activating peptide-induced vascular smooth muscle cell proliferation. J Cardio Vascular Pharmacology,2001;37(5):619-629
[34]Hehtert JM, Dupuy E, Laplace MC, et al. Thrombin induced endothelial cell growth via both a proteolytic and a non-proteolytic pathway. Biochem J, 1994;303P(tl):227-231
[35]Haynes WG,Webb DJ.Endothelin as a regulator of cardiovascular function in health and disease.J Hypertens,1998,16(8):1081-1098.
[36]Baker SJ,Reidy EP.Transducers of life and death:TNF receptor superfamily and associated protein.Oncogene,1996,12:1-9.
[37]Ruiz-Torres A,Lozano R,Melon J,et al.L-calcium channel blockade induced by diltiazem inhibits proliferation,migration and F-actin membrane rearrangements in human vascular smooth muscle cells stimulated with insulin and IGF-1.Int J Clin Pharmacol Ther,2003,41(9):386-91.
[38]Morla AO.Mogford JE.Control of smooth muscle cell proliferation and phenotype by integrin signaling through focal adhesion kinase.Biochem biophys Res Commun,2000,272(1):298-302.
[39]Southgate KM,Fisher M,Banning AP,Thurston Valerie J,Baker Andrew H.Fabunmi Rosalind P,et al.Upregulation of basement membrane degrading metalloproteinase secretion after ballon injury of pig carotid arteries Circ Res, 1996,79(6):1177-1187.
[40]Kyung-Hye Lee,SoYeon Lim,Seok-Min Kang,et al Antiproliferative mechanisms of raxofelast(IRFI-016)in H2O2-stimulated rat aortic smooth muscle cells.European Journal of Pharmacology,2004,484:119-125.
[41]Campbell M,Allen WE,Silversides JA,et al.Glucose-induced phosphati-dylinositol 3-kinase and mitogen-activated protein kinase-dependent uprrgulation of the platelet-derived growth factor-preceptor potentiates vascular smooth muscle cell chemotaxis.Diabetes.2003;52:519-526.
[42]Ahn JD,Morishita R,Kaneda Y,et al.Inhibitory effects of novel AP-1 smooth muscle cell growth and intimal hyperplasia by of P21 and P53.Circ Res.1999;84:543-550.
[43]晋军,祝善俊,祝之明,酪氨酸蛋白激酶抑制剂对自发性高血压大鼠血管平滑肌细胞增殖肥大的影响.岭南心血管病杂志,2003,9(1)：37-40.
[44]田雪梅,李进.动脉粥样硬化平滑肌细胞凋亡相关因素研究进展.医学1998；4(1)：11-14
[45]邓敏,王家富.c-myc与平滑肌细胞增殖和凋亡.国外医学老年医学分册,2001；22(1)
[46]46曾嵘,李进.c-myc结构与功能.国外医学遗传学分册.1997：20(3)116-119
[47]Biros, Ya-minfu Zu-Xiyu. Inhibitory effects of antisense oligodeoxynueleotides targeting c-myc mRNA on smooth muscle cell proliferation andmigration.Proc Nati Acad Sci Usa,1993;90(2):654
[48]Hattori Y,Kakishita H,Akimoto K,Matsumura M,Kasai K.Glycated serum albumin-induced vascular smooth muscle cell proliferation through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by protein kinase C.Biochem Biophys Res Commun 2001;281(4):891-896
[49]Watanabe T,Pakala R,Katagiri T,Benedict CR.Monocyte chemotactic protein1 amplifies serotonin-induced vascular smooth muscle cell proliferation.J Vasc Res 2001;38(4):341-349
[50]Fleckenstein-Grun GCalcium antagonism in vascular smooth muscle cells. Pflugers Arch 1996;432(Suppl):R53-60
[51]Sasaki E,Nozawa Y,Miyoshi K,Kanda A,Yamasaki Y,Miyake H,Matsuura N. TAS-301 blocks receptor-operated calcium influx and inhibits rat vascular smoothmuscle cell proliferation induced by basic fibroblast growth factor and platelet-derived growth factor.Jpn J Pharmacol 2000;84(3):252-8
[52]Velarde V,Jenkins AJ,Christopher J,Lyons TJ,Jaffa AA.Activation of MAPK by modified low-density lipoproteins in vascular smooth muscle cells.J Appl Physiol 2001;91(3):1412-20
[53]Grana X,Reddy EP.Cell cycle control in mammalian cells:role of cyclins,cyclin, dependent kinase(CDKs),growth supperssor genes andcyclin-dependent kinase inhibitors(CKIs).Oncogene 1995; 11:211-219
[54]Simons M,Edelman ER,Rosenberg RD.Antisense proliferation cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid artery injury model.J Clin Invest 1994;93:2351-2356
[55]Luo Y,Hurwitz J,Massague J.Cell-cycle inhibition by independent CDK and PCNA binding domain in p21(CIP 1).Nature 1995;375:159-162
[56]Chen J,Peter R,Saha P.A 39 amino acid fragment of the Cell regulator p21 in sufficient to bind PCNA and partially inhibit replication in vivo.Nuclei Acids Res 1996;24:1727-1737
[2]Molinari BL, Tasat DR, Palmieri MA, O Connor SE, Cabrini RL. Cell-based quantitative evaluation of the MTT assay. Anal Quant Cytol Histol. 2003:25:254-62
[3]Bruggisser R, von Daeniken K, Jundt G, et al. Interference of plant extraets phytoestrogens and antjoxidants with the MTT tetrazolium assay. Planta Med.2002:68:445-8
[4]Chen Y. Yang L, Lee TJ.Oroxylin A inhibition of lipopolysaceharide-ndueed iNOS and COX-2 gene expression via suppression of nuclear factor-kappaB activation. Biochem Pharmacol 2000:59:1445-57:
[5]Chen YC,Shen SC,Lee WR, et al. Emodin induces apoptosis in human promyeloleukemic HL-60 cells accompanied by activation of Caspase3 Caseade but independent of reactive oxygen species production. Biochem Pharmacol2002;64:1713-24;
[1]Yao C,Wu Z, Wu Y. The changing pattern of cardiovascular disease inChina. World Health Stat Q.1993:46(2):113-8
[2]Brophy JM, Belisle P, Joseph L.Evidence for use of coronary stents. A hierarchical Bayesian meta-analysis. Ann Intern Med 2003;138(10):777-86.
[3]Park SW, Lee CW, Hong MK, Kim JJ, Cho GY, Nah DY,Park SJ.. Randomized comparison of coronary stenting with optimal balloon angioplasty for treatment of lesions in small coronary arteries.Eur Heart J,2000:21 (12):1785-9.
[4]Sanchez PL, Rodriguez-AlemParte M, Colon-Hernandez PJ, et al. Directional coronary atherectomy vs rotational atherectomy for the treatment of in-stent restenosis of native coronary arteries.Catheter Cardiovasc Interv. 2003:58:155-61.
[5]Nakatani M, Takeyama Y, Shibata M, et al. Mechanisms of restenosis after coronary intervention:difference between plain old balloon angioplasty and stenting. Cardiovasc Pathol.2003; 12:40-8
[6]Fattori R, Piva T. Drug-eluting stents invascular intervention. Lancet.2003; 361(9353):2470-9
[7]Hanke H, Strohschneider T, Obethoff M, Betz E, Karsch KP. Time course of smooth muscle cell proliferation in the intima and media of arteries following experiment alangioplasty.CircRes.1990:67(3):651-9
[8]Bennett MR, O Sullivan M. Mechanisms of angioplasty and sten restenosis: implications for design of rational therapy.Pharmacol Ther 2001;91(2):149-66
[9]Wang Z, Hsieh TC, Zhang Z, Ma Y, WU JM. Identification and purification of resveratrol targeting proteins using immobilized resveratrol affinity chomatography. Bio Chemical and biophysical research communications. 2004:323(3):743-749.
[10]Sun K, Al-Regaiey M. Mastemak B, et al. Local expression of GH and IGF-1 in the hippocampus of GH-deficient long-lived mice. Neuro biology of Aging, 26(6)929-937.
[11]Shimizu M, Deguehi A, Hara Y, et al. EGCG inhibits activation of the insulin-like growth factor-1 receptor in human colon cancer cells. Biochem Biophys Res Commun 2005:334:947-953.
[12]Hehtert JM, Dupuy E, Laplace MC, et al. Thrombin induce endothelial cell growth via both a proteolytic and a non-proteolytic pathway. Biochem J,1994:303(ptl):227-231.
[13]Yohsida Y, Mitsumata M, Yamane T. Moprhology and increase growth rate of atherosclerotic intimal smooth-muscle cells. Arch Pathol Lab Med,1988, 112:987-996.
[14]Vu TK, Hunag DT, Wheatno VI, et al. Molecular cloning of a functional thrombni recpetor reveals a novel proteolytic mechanism of recpetor activition.Cell,1991:64(6):1057-068.
[15]McNamara CA, Sarembock JJ, Gmple IW, et al. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated recpetor. J Clin Invest,1993:91 (1):94-98.
[16]王启贤,吕俊升.凝血.酶对大鼠血管平滑肌细胞血小板源性生长因子基因表达的影响.¨中国动脉硬化杂志,2000,8(：)126-31.
[17]Steffen Bassus, Olaf Herkert, Nicola Kronemann. Thrombin causes vascular endothelial growth factor expression in vascular smooth muscle cells.Arterioscler thromb vase Biol,2001,21 (9):1550-1555.
[18]Walton SP, Stephanopoulos GN, Yarmush ML, et al. Thermodynamic nand kinetic-characterization of oligodexynucleotide binding to a structured mRNA. J Bio Phys,2002,82(1):366-377
[19]Seiler SM. Thombin receptor antagonists. Semin thromb Hemost 1996:22(3):223-232.
[20]Bennett MD, Evan GI, Schwarz SM. Apoptosis of rat vascular smooth muscle cells is regulated by p53-dependent and -independent pahtways. Cicr Res, 1995,77:266
[21]Inagaki Y, Yamagishi S, Amano S, et al. Interferon gamma induced apoptosis and activation of THP-1 macrophages. Life Sci.2002 Oct 11;71(21):2499
[22]Miyashita T, Reed JC.Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell,1995 Jan 27;80(2):293
[23]姜泊.细胞凋亡基础与临床.北京：人民军医出版社,1997.167
[24]Matsusaka T.Ichikawa I.Biological functions of angiotensin and its receptors. Annual Review of Physiology,1997.59:395-412.
[25]Hanada M.Saito E.Kambe T,et al.Evidence for the involvement of platelet-derived growth facto in the angiotensin-induced growth of rat vascularsmooth muscle cells.Biol Pharm Bull,1999.22(2):137-141.
[26]Mondrof UF,Geiger H,Herrero M.et al.Involvement of the platelet-derived growth factor receptor in angiotensin-induced activation of extracellular regulated dinases 1 and 2 in human mesangial cells.FEBS Lett.2000. 72(1):129-132.
[27]Touyz RM,HeqDeng LY,Schiffrin EL.Role of extracellular signal-regulated kinases in angiotensin Ⅱ-stimulated contraction of smooth muscle cells from human resistance vessels.Circulation.1999.99:392-399.
[28]Touyz RM,He El Mabrouk M.et al.Diferential activation of ERK1/2 and p38MAP kinase by angiotensin II type I receptor in vascular smooth muscle cells from WKY and SHR.Journal of Hypertension.2001.19:553-559.
[29]Touyz RM,Wu XH.Heq,et al.Role of c-Src in the regulation of vascular contraction and Ca2+ signaling by angiotensin II in human vascular smooth muscle cells.Journal of Hypertension.2001.19:441-449.
[30]Hsueh WA.Do YS.Anderson PW,et al.Angiotensin H in cell growth and matrix production.Advances in Experimental Medicine and Biology,1995.377:217-223.
[31]Thomas SM.Brugge JS.Cellular functions regulated by Src family kinases. Annual Review of Cell Division.1997.13:513-609.
[32]Ihle JN.Cytokine receptor signaling.Nature.1995.377:591-594.
[33]Fabio Rossi.Cora Bertone.Silvia Pctricca,et al.Adrenomedullin antagonizes angiotensin Ⅱ-stimulated proliferation of human aortic smooth muscle cells. Peptides,2006,(27):2935-2941.
[34]张玉珍.高平进.王兴宇,等.血管紧张素Ⅱ对血管平滑肌细胞增殖的影响.中国病理生理杂志,2000.16(10)：1007.
[35]Anger M.Lompm AM.Valot O.et al.Cellular distribution of Ca2+ release channels in rat cardiac hypertrophy induced aortic stenosis.Circulation. 1998:98(22):2477-2486
[36]Lee HW.Eghbali WM.Estrogen enhances proliferative capacity of cardiac fibroblasts by estrog receptor-and mitogen-activated protein kinase-dependent pathways.J Mol Cell Cardiol.1998.30(11):1359-368
[37]Rabikin SW.Sunga PS.Sanghera JS.et al.Reduction of angiotensin Ⅱ-induced activation of mitogen-activated ptotein kinase in cardiac hypertrophy[J].Cell Mol Life Sci.1997:53(11):955-959
[38]Pinton P.Ferrari D,Papizzi Z,et al.The Ca2+ concentration of the endoplasmic reticulum is a key determinant of ceramide-induced apoptosis:significance for the molecular mechanism of Bcl-2 action.EMBO J.2001:20:2690-2701.
[1]Detre K, Holubkov R, Kelsey S, et al. Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981.The National Heart, Lung and Blood Institute Registry. N Engl J Med 1988:318:265-270.
[2]Kurbaan AS, Bowker TJ, Iisley CD, Riekards AF. Impact of postangioplasty restenosis on comparisons of outcome between angioplasty and bypass grafting. Coronary AngioPlasty versus Bypass Revascularisation Investigation (CABRI) Investigators.Am J Cardiol.1998:82:272-6
[3]Serruys PW, Unger F, Van Hout BA, et al. The ARTS study(Arterial Revaseularization Therapies Study). SeminInteryCardiol.1999:4:209-19
[4]Fischman DL. L eon MB, Baim DS, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Resteno sis Study Investigators. N Engl J M ed.1994,331 (8):496-501.
[5]Elezi S. Kastrat iA.N eumann FJ. et al. Vessel size and longterm outcome after coronary stent placement.Circulat ion,1998:98:1875-1880.
[6]Chervu A, Moore WS. An overview of intimal hyperplasia. Surg Gynecol Obstet.1990:171:433-7.
[7]Heekenkam PJ, Gawenda M, Brunkwall J. Vascular restenosis. Basic Science and clinical implications. J Cardiovase Surg(Torino).2002;43:349-57
[8]Surh YJ. Anti-tumor promoting potenial of selected spice ingredients with antioxidative and anti-inflammatory activities:a short review. Food Chem Toxicol,2002,4(8):1091
[9]Aggarwal BB, Kumar A, Bharti AC. Anticancer potential of curcumin:preclinical and clinical studies.AnticancerRes,2003,23(1A):363
[10]李冬保.动脉粥样硬化和在狭窄中平滑肌细胞的凋亡与增殖.国外医老年医学分册,2000;32(1)8
[11]M.R.Benett, GI Even. Apoptosis of rats smooth muscle cell is regulated by P53 dependent and independent Pathway. Imperial cancer research,2000:12(4)45 sehisandrinBandemodin.PlantaMed2002:68:951-6
[12]12 Vousden KH. Activation of the P53 tumor suppressor Protein. Biochimica Bio Physica Acta2002; 1602:47-59
[13]Sharpless NE.Depinho RA. P53:good cop/bad cop.Cell2002:110:9-12
[14]Yang J, Duerksen- Hughes P. A new approach to identifying genotoxic carcinogens:P53 induction as an indicator of genotoxic damage. Carcinogenesis.1998:19:1117-1125
[15]SattlerM.Liang H.Nettesheim D.et al.Structure of Bcl-XL-Bax Peptide Complex:Recognition between regulators of apop tosis.Science.1997.275(5302):983
[16]Tsujimoto Y.Croce CM.Analysis of the structure.transcrip ts.and protein product of bcl-2.the gene involved in human follicular lym2 phoma.PN AS.1986.83(14):5214-5218
[17]王祥贵,冯义柏.朱利民,等.同型半胱氨酸对人血管平滑肌细胞凋亡及bax、bcl-2表达的影响中国全科医学2005年3月第8卷第6期743
[1]Huast DA, More RH, Movat HZ. The role of smooth muscle cells in the fibrogenesis of atherosclerosis. American journal pathology,1960,37:377-387.
[2]Schwartz SM, CamPbell GR, Campbell JH. Replication of smooth muscle cells in vascular disease. Circulation Research,1986,58:427-444.
[3]Murrya TR, Marshall BE, Macarak EJ. Constraction of vascular smooth muscle in cell culutre. Journal cell physiology,1990,143:26-38.
[4]韩启德,文允锐.血管生物学.北京：1997,北京医科大学、中国协和医科大学联合出版社.
[5]Hehtert JM, Dupuy E, Lpalace MC, et al. Thrombin induce endohthelial cell growth via both a proteolytic and a non- proteolytic pathway. Biochme J, 1994;303(ptl):227-231
[6]Yohsida Y, Mitsmuata M, Yamane T. Moprhology and increase growth rate of atherosclerotic intimal smooth-muscle cells. Arch Pathol Lab Med,1988, 112:987-996
[7]Vu TK, Huang DT, Wheaton VI, et al. Molecular cloning of a fuctional thrombin recpetor reveals a novel proteolytic mechanism of recpetor activition.Cell,1991;64(6):1057-068
[8]McNamara CA, Sarembock U, Gmple IW, et al. Thrombin stimulates proliefartion of cultured rat aortic smooth muscle cells by a porteolytically activated recptor.J Clin Invest,1993:91(1):94-98
[9]工启贤,吕俊升.凝血酶对大鼠血管平滑肌细胞血小板源性生长因子基因表达的影响.中国动脉硬化杂志,2000,8(1)：26-31
[10]Steffen Bassus, Olaf Herkert, Nicola Kronmeann. Thrombin causes vascular endothelial growth factor expression invascular smooth muscle cells. Arterioscler thromb vasc Biol,2001,21(9):1550-1555
[11]Walton SP, Stephanopoulos GN, Yarmush ML, et al. Thermodynamic and kinetic-characterization of oligo dexynucleotide binding to a structured mRNA. J Bio Phys,2002,82(1):366-377
[12]宪敏,米立国,赵秀文,等.反义TR和p21双基因共同表达对人主动脉平滑肌细胞增殖与凋亡的作用.中国医学科学院学报,2002；24(：4)339-342
[13]Bennett MD, Evan GI, Schwarz SM. Apoptosis of rat vascular smooth muscle cells is regulated by P53-dependent and-in dependent pahtways. Cicr Res, 1995,77:266
[14]Inagaki Y, Yamagishi S, Amano S, et al. Interferon gamma induced apoptosis and activation of THP-1 macrophages. Lifd Sci.2002 oct11;71(21):2499
[15]Miyashita T, Reed JC.Tumor supperssor P53 is a direct transcriptional activator of the human bax gene. Cell,1995 Jan27;80(2):293
[16]姜泊.细胞凋亡基础与临床.北京：人民军医出版社,1997.167
[17]李冬宝(综述),谢苗荣(审校).动脉粥样硬化与再狭窄中平滑肌细胞的调亡与增殖.2003；20(1)41
[18]Paula Bray, Alex Agrotis, Alex Bobik. Transforming Growth Factor-β and receptor Tyrosine Kinase-Activating Growth Factors Negatively Regulate Collagen Genes in Smooth muscle of Hypertensive Rats. Scienttific contribtion,1999
[19]Okura T, Lgasem, ETC. Platelet derived growth factor induces apoptpsis invascular smooth muscle cell:roles of the BCL-2 family. Circulation,2001
[20]朱中生(综述),王晋明(审校).高血压性动脉硬化的发生机制研究进展.岭南心血管杂志,2001；10(1)18
[21]Nikol S,Weir L,Sullivan A,et al.Persistently in creased expression of the transforing growth factor-beta Ⅰ gene in human vascular restenosis:Analysis of 62 patiants with one or mine episocles of restenosis.Cardiovasc Pathol 1994;3:57-64
[22]郭庆,温进坤.碱性纤维母细胞生长因子对血管平滑肌细胞增殖的影响.中国动脉硬化杂志,1996,4：168-171
[23]石缨,温进坤.新生小牛血清、碱性成纤维细胞生长因子和肝素对大鼠血管平滑肌细胞骨桥蛋白表达的影响.中国动脉硬化杂志,1996,7：1-3
[24]周秀霞,温进坤,韩梅.含活血化癖中药血清对血管平滑肌细胞迁移相关基因表达的影响.河北医科大学学报,2000,21：217
[25]石缨,温进坤.新生小牛血清、碱性成纤维细胞生长因了和肝素对大鼠血管平滑肌细胞迁移的影响.中国动脉硬化杂志,1998,6：189-192
[26]邢东琦,高广道.Ang的胞内信号转导径路[J].国外医学生理、病理科学与临床分册.1998；18(3)：233-236
[27]Xiao F, Puddefoot JR,Barker S,Mechanism for aldosterone potential-tionof angiotensin Ⅱ-stimulated rat arterial smooth muscle cell proliferation. Hypertension.2004;44:340-345.
[28]工启贤,吕俊升.凝血酶对大鼠血管平滑肌细胞血小板源性生长因子基因表达的影响.中国动脉硬化杂志,2000,8(：)126-31
[29]Steffen Bassus, Olaf HerkCrt, Nicola Kronmeann. Thrombin causes vascular endothelial growth factor expression in vascular smooth muscle cells.Arterioscler throm vasc Biol,2001,21(9):1550-1555
[30]任国峰,王宗立,李拥军,等.反义大鼠凝血酶受体基因的构建及其对主动脉血管平滑肌细胞增生的作用.基础医学与临床,2000；20(3)：47
[31]Nelken NA, Soifer SJ, O'keeef J,et al. Thrombin receptor expression in nomral and arterioscler human arteries. J Clin Ivest,1992;90(4):1614-1621
[32]Wilocx JN, Rodriguez J, Subramanian R, et al. Characterizaton of thrombin receptor expression furing. Circ Res,1994;75(6):1029-1038
[33]Pakala R, Liang CT, Benedict CR. A peptide analogue of thrombin receptor-activating peptide-induced vascular smooth muscle cell proliferation. J Cardio Vascular Pharmacology,2001;37(5):619-629
[34]Hehtert JM, Dupuy E, Laplace MC, et al. Thrombin induced endothelial cell growth via both a proteolytic and a non-proteolytic pathway. Biochem J, 1994;303P(tl):227-231
[35]Haynes WG,Webb DJ.Endothelin as a regulator of cardiovascular function in health and disease.J Hypertens,1998,16(8):1081-1098.
[36]Baker SJ,Reidy EP.Transducers of life and death:TNF receptor superfamily and associated protein.Oncogene,1996,12:1-9.
[37]Ruiz-Torres A,Lozano R,Melon J,et al.L-calcium channel blockade induced by diltiazem inhibits proliferation,migration and F-actin membrane rearrangements in human vascular smooth muscle cells stimulated with insulin and IGF-1.Int J Clin Pharmacol Ther,2003,41(9):386-91.
[38]Morla AO.Mogford JE.Control of smooth muscle cell proliferation and phenotype by integrin signaling through focal adhesion kinase.Biochem biophys Res Commun,2000,272(1):298-302.
[39]Southgate KM,Fisher M,Banning AP,Thurston Valerie J,Baker Andrew H.Fabunmi Rosalind P,et al.Upregulation of basement membrane degrading metalloproteinase secretion after ballon injury of pig carotid arteries Circ Res, 1996,79(6):1177-1187.
[40]Kyung-Hye Lee,SoYeon Lim,Seok-Min Kang,et al Antiproliferative mechanisms of raxofelast(IRFI-016)in H2O2-stimulated rat aortic smooth muscle cells.European Journal of Pharmacology,2004,484:119-125.
[41]Campbell M,Allen WE,Silversides JA,et al.Glucose-induced phosphati-dylinositol 3-kinase and mitogen-activated protein kinase-dependent uprrgulation of the platelet-derived growth factor-preceptor potentiates vascular smooth muscle cell chemotaxis.Diabetes.2003;52:519-526.
[42]Ahn JD,Morishita R,Kaneda Y,et al.Inhibitory effects of novel AP-1 smooth muscle cell growth and intimal hyperplasia by of P21 and P53.Circ Res.1999;84:543-550.
[43]晋军,祝善俊,祝之明,酪氨酸蛋白激酶抑制剂对自发性高血压大鼠血管平滑肌细胞增殖肥大的影响.岭南心血管病杂志,2003,9(1)：37-40.
[44]田雪梅,李进.动脉粥样硬化平滑肌细胞凋亡相关因素研究进展.医学1998；4(1)：11-14
[45]邓敏,王家富.c-myc与平滑肌细胞增殖和凋亡.国外医学老年医学分册,2001；22(1)
[46]46曾嵘,李进.c-myc结构与功能.国外医学遗传学分册.1997：20(3)116-119
[47]Biros, Ya-minfu Zu-Xiyu. Inhibitory effects of antisense oligodeoxynueleotides targeting c-myc mRNA on smooth muscle cell proliferation andmigration.Proc Nati Acad Sci Usa,1993;90(2):654
[48]Hattori Y,Kakishita H,Akimoto K,Matsumura M,Kasai K.Glycated serum albumin-induced vascular smooth muscle cell proliferation through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by protein kinase C.Biochem Biophys Res Commun 2001;281(4):891-896
[49]Watanabe T,Pakala R,Katagiri T,Benedict CR.Monocyte chemotactic protein1 amplifies serotonin-induced vascular smooth muscle cell proliferation.J Vasc Res 2001;38(4):341-349
[50]Fleckenstein-Grun GCalcium antagonism in vascular smooth muscle cells. Pflugers Arch 1996;432(Suppl):R53-60
[51]Sasaki E,Nozawa Y,Miyoshi K,Kanda A,Yamasaki Y,Miyake H,Matsuura N. TAS-301 blocks receptor-operated calcium influx and inhibits rat vascular smoothmuscle cell proliferation induced by basic fibroblast growth factor and platelet-derived growth factor.Jpn J Pharmacol 2000;84(3):252-8
[52]Velarde V,Jenkins AJ,Christopher J,Lyons TJ,Jaffa AA.Activation of MAPK by modified low-density lipoproteins in vascular smooth muscle cells.J Appl Physiol 2001;91(3):1412-20
[53]Grana X,Reddy EP.Cell cycle control in mammalian cells:role of cyclins,cyclin, dependent kinase(CDKs),growth supperssor genes andcyclin-dependent kinase inhibitors(CKIs).Oncogene 1995; 11:211-219
[54]Simons M,Edelman ER,Rosenberg RD.Antisense proliferation cell nuclear antigen oligonucleotides inhibit intimal hyperplasia in a rat carotid artery injury model.J Clin Invest 1994;93:2351-2356
[55]Luo Y,Hurwitz J,Massague J.Cell-cycle inhibition by independent CDK and PCNA binding domain in p21(CIP 1).Nature 1995;375:159-162
[56]Chen J,Peter R,Saha P.A 39 amino acid fragment of the Cell regulator p21 in sufficient to bind PCNA and partially inhibit replication in vivo.Nuclei Acids Res 1996;24:1727-1737