摘要
目的:基于王永炎院士的“证候概念及其属性”及田金洲教授提出的“证候靶位及表征”理论,研究血瘀证与颈动脉血流动力学、颈动脉粥样硬化斑块及其活性物质的关系,探讨CAS与血瘀证的相关性。
方法:对来源于中国人民解放军第306医院的136例脑梗死组患者及73例对照组人群进行中医证候要素评分及颈动脉彩色多普勒超声检查,并用ELISA法检测脑梗死患者血清MMPS-9、TIMP-1、b-FGF及Hs-CRP的含量。
结果:(1)血瘀证与颈动脉血流动力学的相关性:a.在脑梗死患者中,血瘀证组的右侧颈动脉、左CCA、ICA内径均显著大于非血瘀证组(P <0.01/0.05),血瘀证与双侧颈动脉内径呈显著正相关(P <0.01)。在对照人群中,血瘀证组的双侧CCA内径均大于非血瘀证组(P <0.05),血瘀证与左CCA内径有相关性(P <0.05)。脑梗死血瘀证组的双侧颈动脉内径显著大于对照血瘀证组(P <0.01)。b.在总体人群中,血瘀证组的右CCA的IMT显著大于非血瘀证组(P <0.01)。在脑梗死患者中,血瘀证组的右ECA、左CCA及左ICA的IMT大于非血瘀证组(P <0.05),血瘀证与颈动脉粥样硬化呈正相关(P <0.05)。脑梗死血瘀证组的颈动脉硬化、IMT增厚率、左ICA的IMT大于对照血瘀证组(P <0.05)。c.在总体人群中,血瘀证组双侧ECA收缩期流速、右CCA的PI小于非血瘀证组(P <0.01/0.05),左CCA舒张期流速大于非血瘀证组(P <0.05)。脑梗死血瘀证组双侧ECA、右ICA收缩期流速,双侧CCA、右ECA的RI、双侧CCA、右ECA的PI大于对照血瘀证组(P <0.01/0.05)。总体血瘀证与双侧ECA收缩期流速、右CCA、右ECA的PI呈负相关(P <0.01/0.05),与左CCA舒张期流速呈正相关(P <0.01)。对照血瘀证与右CCA舒张期流速呈正相关(P <0.05)。(2)血瘀证与颈动脉粥样硬化斑块的相关性:a.在脑梗死患者中,血瘀证组颈动脉斑块不匀质、不规则率高于非血瘀证组(P <0.05)。脑梗死血瘀证组颈动脉斑块有无、数目、不规则及不匀质率大于对照血瘀证组(P <0.01)。总体血瘀证与颈动脉斑块形态呈正相关(P <0.05)。脑梗死血瘀证与斑块数目、性质呈正相关(P <0.05)。b.在脑梗死患者中,血瘀证的颈动脉狭窄及多支狭窄率较非血瘀证显著增高(P <0.01)。脑梗死血瘀证组的颈动脉狭窄及多支狭窄率高于对照血瘀证组(P <0.01)。脑梗死血瘀证与颈动脉狭窄、狭窄支数呈正相关(P <0.01)。(3)血瘀证与颈动脉粥样硬化活性物质的相关性:脑梗死患者血清MMP-9比较,血瘀证组较非血瘀证组显著升高(P <0.01),血瘀证与血清MMP-9呈正相关(P <0.01)。
结论:1.血瘀证与动脉粥样硬化呈正相关。2.血瘀证与颈动脉内径、斑块的形态及数目呈正相关,且其斑块具有不稳定性。在发生脑梗死时,斑块数目增加、不稳性增高。3.血瘀证存在颈动脉内径增大、IMT增厚、部分颈动脉狭窄及血流速度改变,在发生脑梗死时颈动脉内径明显增大,IMT增厚及颈动脉狭窄的程度加重,狭窄支数增多。4.脑梗死血瘀证与血清MMP-9呈正相关。
OBJECTIVE: According to the new theory of“the conception and attribute of the sndyrome”, this study is to observe the relationship between the Blood Stasis Syndrome(BSS) defined by Chinese medicine with carotid hemodynamics, carotid atherosclerotic plaques(CAP) and atherosclerotic relative active substances, to look for correlation between atherosclerosis(AS) with BSS.
METHODS: 209 patients were selected from 306th Hospital of The Chinese People’s Liberation Army .All subjects comprised 136 patients with acute cerebral infarction(CI) and 73 volunteers without acute cerebral infarction. All patients were examined color dopplor ultrasound for hemodynamics ,IMT and CAP of carotid artery. Morever,ELISA way was used to test the levels of MMPS-9,TIMP-1,b-FGF , Hs-CRP and blood-lipid in blood-serum in CI patients.
RESULTSL1)The correlation between BSS and carotid hemodynamics:Ⅰ.The carotid diameter, intima-media thickness(IMT) of BSS group is more than none- Blood Stasis Syndrome(NBSS) group(P <0.01/0.05). and also the carotid velocity, Resistance indexes(RI), Pulsatile indexes(PI) of several carotid artery in BSS group is more than NBSS group(P <0.01/0.05),but the carotid velocity of several carotid artery of BBS group is less than NBBS group (P <0.01/0.05).Ⅱ:There is correlation between carotid diameter, AS, diastolic velocities of several carotid artery with BSS(P <0.01/0.05).contraily, systolic velocity of several carotid artery, PI has a negative correlation with BSS(P <0.01/0.05).(2) The correlation between BSS and CAP:Ⅰ.The frequency of ulcerative CAP in BSS group is higher than NBSS group(P <0.05).The frequency of ulcerative and heterogeneous CAP in patients with BSS and CI are more than those patients without BSS have CI(P <0.01/0.05). There is correlation between the quantity of CAP and ulcerative CAP with BSS(P<0.05).Ⅱ.Carotid atherosclerotic stenosis(CAS) and the quantity of CAS in BSS group is more than NBSS group (P <0.01/0.05). The frequency of CAS in patients with BSS and CI are much more than those patients without BSS have CI(P <0.01). There is significant correlation between the quantity of CAS and CAS with BSS(P<0.01).(3) The correlation between BSS and atherosclerotic relative active substances:The levels of MMP-9 in blood serum in patients with CI have BSS is much more than those patients without BSS have CI(P<0.01). There is significantly correlation between MMP-9 with BSS(P<0.01).Comparing to NBSS group, the levels of TIMP-1,b-FGF and Hs-CRP in blood serum in BSS group are no significantly difference(P >0.05). There is no signifantly difference between TIMP-1,b-FGF , Hs-CRP, blood-lipid with BSS(P >0.05).
CONCLUSIONL1)The patients with BSS have AS. (2)There is correlation between carotid diameter,the number of CAP and ulcerative CAP with BSS.Morever, the CAP in patients with BSS have unstablity. The number and unstablity of CAP increased in patients with BSS have CI.(3) The carotid diameter of patients with BSS have increased,and also the patients with BSS have CAS and abnormal carotid hemodynamics. The carotid diameter,the degree of CAS and number of CAS increased in paitents with BSS have CI.(4)There is correlation between MMP-9 with BSS.Contrarily,there are no correlation between TIMP-1,b-FGF , Hs-CRP, blood-lipid with BSS.
引文
1 方向华. 中国卒中的流行现状及其影响因素.中国脑血管病杂志. 2004,1(5):233-237
2 中国卫生年鉴. 北京. 人民卫生出版社. 2002: 484-485
3 王兆钺. 血栓相关性疾病的临床流行病学. 中华医学杂志 2004;84(5):432-434
4 梁伟雄,黄培新,刘茂才,等.中风病急性期中医证候分布规律的研究.广州中医药大学学报,1997,14(2):71-75
5 高颖,吴燕,任占利,等.216 例腔隙性脑梗塞中医证候学观察及临床资料分析.中国中医药信息杂志,2000, 10 (7):29-30
6 姚魁武,王 阶,陈可冀.血瘀证量化诊断及病证结合研究.学位论文.北京:中国中医研究院,2001
7 蔡钦朝,汪琼华,吴云智.血瘀证患者血管内皮内分泌功能的观察.安徽中医学院学报,1998,17(2):61-62.
8 石志芸,施赛珠,陈剑秋,等. 中医血瘀证与血栓相关分子标志物的研究.中医研究,2003,16(6):21-22
9 孙锡印,杨妻琳.冠心病气滞血瘀与气虚血瘀证型间血载脂蛋白的异同及辨治影响.江苏中医,1997,18 (6)
10 李林森,田金洲,蔡艺灵等.215 例急性脑梗死患者凝血因子变化与血瘀证的相关性研究,2007,26(10):642-646
11 郭 蕾,王永炎,张志斌.关于证候概念的诠释.北京中医药大学学报, 2003, 26 (2) : 5~8
12 田金洲,王永炎,时晶等.证候的概念及其属性.北京中医药大学学报.2005, 28 (5):6~8
13 Palak J, Shemanski L, O Leary, et al. Relationship between incident stroke and the severity of internal carotid stenosis. Circulation, 1994, 90(PartⅡ): 1399-1404
14 Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis JAMA. 1995. 273: 1421-1428
15 Allan PL, Mowbray PI, Lee AJ, et al. Relationship between carotid intima-media thickness and symptomatic and asymptomatic peripheral arterial disease, Stroke, 1977,28:348-353
16 El-Barghouty NM,Levine T,Ladva S,et al.Histological verification of computerized carotid plaque characterization.Eur J Vac Endovasc Surg.1996,11:414-416
17 Wilhjelm JE,Gronholdt MLM,Wiebe BM,et a1.Quantitative analysis of ultrasound B-mode image of carotid atherosclerotic plaquexorrelation with visual classification and histological examination.IEEE Trans Med Imaging, 1998,17:910-922
18 Lemaitre V, Amiento JD. Matrix metalloproteinase in development and disease.Birth Defects Res C Embryo Today,2006,37(7):1731-1736
19 Zhang X,Chirstenson LK, Nothnick WB,Regulation of MMP-9 expression and activity in the mouse uterus by estrogen. Mol Reprod Dev,2007,74(3):321-331
20 Rouis M,Adamy C,Duverger N,et al. Adenovious-mediated overexpression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice.Circulation,1999,100(5):533-540
21 Gospodarovvicz D,et al. Fgf proc natl acad sci USA,1984,81:6963-6967
22 陈灏珠,杨昌生.动脉粥样硬化.见:陈灏珠主编.实用内科学,第十二版.北京:人民卫生出版社,2004:1459-1467
23 Yeh ET. High-sensitivity C-reactive protein as a risk assessment tool for cardiovascular disease. Clin Cardiol,2005,28(9):408-412
24 武月萍.血瘀证的危险因素及其与疾病的相关性研究.北京中医药大学博士研究生论文.2006
25 朱爱华.炎症反应与急性脑梗塞血瘀证的相关性研究.北京中医药大学博士研究生论文.2007
26 倪敬年.脑梗塞患者血瘀证与颈动脉粥样硬化的相关性研究.北京中医药大学硕士研究生论文.2007
27 田金洲,时晶,倪敬年等.脑梗塞患者颈动脉斑块与血瘀证的相关性研究.中华中医药杂志.2007,22(3):149-152.
1. North American Symptomatic Carotid Endaterectomy Trail Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis .N Eeg J Med, 1991, 325:445-453
2. European Carotid Surgery Trails Collabrative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis final results of the MRC European Carotid Surgery Trial(ECST). Lancet,1998,351:1379-1387
3. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Endarterectomy for asymptomatic carotid artery stenosis JAMA. 1995,273:1421-1428
4. 王顺道,杜梦华,谢庆凡等.中风病急性期证候演变规律的研究.中国中医急症 1996,5(3):121-124
5. 田金洲,韩明向,涂晋文,杨承芝,杨惠民,邹忆怀,刘峘.《血管性痴呆的诊断、辨证及疗效评价标准》.北京中医大学学报,2001,23(5);24-30.
6. 华扬,刘蓓蓓,凌晨等,超声检查对颈动脉狭窄 50~60%和 70~99%诊断准确性的评估. 中国脑血管病杂志. 2006,3(5):211-218
7. Grant EG, Benson CB, Moneta GL, et al. Carotid artery stenosis grayscale and Doppler ultrasound diagnosis-society of radiologists in ultrasound consensus conference. Ultrasoud Q.2003,19:190-198
8. 徐智章等.外周血管超声彩色血流成像.北京:人民卫生出版社 ,2002.95
9. Rongling LI,Bruce B,Patricia A,etal.B-mode-detected carotid artery plaque in a general population.Stroke,1994,25:2377-2383.
10. 丁建平,华扬,王拥军. 颈动脉粥样硬化的超声诊断及价值.国外医学脑血管病分册, 2002,8(1):26-29
11. 李建初主编.血管和表浅器官彩色多普勒超声诊断学. 北京: 北京医科大学、中国协和医科大学联合出版社, 1999: 87-92
12. Steinke W, Els T, Hennerici M. Compensatory carotid artery dilation in early atherosclerosis. Circulation, 1994, 89: 2578-2581.
13. Pasterkamp G, Wensing PJW, Post MJ, et al. Paradoxical arterial wall shrinkage may contribute to luminal narrowing of human atherosclerotic femoral arteries Circulation, 1995, 91: 1444-1449.
14. Labropoulous N, Zarge J, Mansour A, et al. Compensatory arterial enlargement is a common pathophysiologic response in early atherosclerosis. Am J Surg,1998,176:140-143.
15. Glagov S, Weisnebery E, Zanns CK, et al. Compensatory enlargement of human atherosclerotic coronary arteries. N Eng J Med, 1987, 316: 1372
16. 张梅,张运,戴晓华等.颈动脉粥样硬化血管重构及其后效影响因素的研究.中国超声医学杂志,2003, 19 (5): 334-336.
17. Yasaki Y, Kawamori R, Matsusima H, et al. Asymptomatic hyperlycamia is associated with increasedintemal plus media thickness of carotid artery. Diabetologia, 1995, 38: 585-591
18. Mannami T,Konishi M,Baba S , et al. Prevalence of asymptomatic carotid atherosclerotic lesions detected by high-resolution ultrasonography and its relation to cardiovascular risk factor in the general population of a Japanese city. The Suita Study. Stroke. 1977, 28: 518-525
19. Bond MG, Wilmonth SL, Enevold GL, et al. Detection and monitoring of asymptomatic atherosclerosis clinical trail. Am J Med, 1989,86: 33-36.
20. 华扬,编著. 实用颈动脉和颅脑血管超声诊断学.北京科学出版社, 2002,8
21. 王炼主编.临床彩色多普勒超声诊断.南京,航空工业出版社,1996,129-132.
22. Basket,Nance DR, Karmel MI,et al. Screening for carotid junction disease by spectral analysis of Doppler signals. Cardiovascular Res,1997, XI:147-149
1. Palak J, Shemanski L, O Leary, et al. Relationship between incident stroke and the severity of internal carotid stenosis. Circulation, 1994, 90(PartⅡ): 1399-1404
2. Rachael A. Wyman, MD, Michael C. Fraizer, MD, Jon G. Keevil, MD,et al Ultrasound-detected carotid plaque as a screening tool for advanced subclinical atherosclerosis. American Heart Journal.2005. 150( 5):1081-1085
3. Langsfield M,Gray-Weale AC,Lusby RJ.The role of plaque morphology and diameter reduction in the development of new symptoms in asymptomatic carotid arteries.Vas Surg,1989,20:844-849
4. Gronholdt MLM,Nordestgaard BGSchroeder TV et al.Ultrasound echolucent carotid plaques predict future stroke.Circulation,2001,104:68-73
5. 田金洲,韩明向,涂晋文,杨承芝,杨惠民,邹忆怀,刘峘.《血管性痴呆的诊断、辨证及疗效评价标准》.北京中医大学学报,2001,23(5):24-30.
6. 华扬,刘蓓蓓,凌晨等,超声检查对颈动脉狭窄 50~60%和 70~99%诊断准确性的评估. 中国脑血管病杂志. 2006,3(5):211-218
7. Grant EG, Benson CB, Moneta GL, et al. Carotid artery stenosis grayscale and Doppler ultrasound diagnosis-society of radiologists in ultrasound consensus conference. Ultrasoud Q.2003,19:190-198
8. 徐智章等.外周血管超声彩色血流成像.北京:人民卫生出版社 ,2002.95
9. Rongling LI,Bruce B,Patricia A,etal.B-mode-detected carotid artery plaque in a general population.Stroke,1994,25:2377-2383.
10. 华扬,编著. 实用颈动脉和颅脑血管超声诊断学.北京科学出版社, 2002,8
11. 丁建平,华扬,王拥军. 颈动脉粥样硬化的超声诊断及价值.国外医学脑血管病分册, 2002,8(1):26-29
12. North American Symptomatic Carotid Endaterectomy Trail Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis .N Eeg J Med, 1991, 325:445-453
13. European Carotid Surgery Trails Collabrative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis final results of the MRC European Carotid Surgery Trial(ECST). Lancet,1998,351:1379-1387
14. Grant EG, Benson CB, Moneta GL, et al. Carotid artery stenosis grayscale and Doppler ultrasound diagnosis-society of radiologists in ultrasound consensus conference. Ultrasoud Q.2003,19:190-198
15. Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation, 2001, 104: 365-372
16. Shan PK. Pathophysiology of coronary thrombosis: role of plaque rupture and plaque erosion. Prog Cardiovase Dis, 2002, 44: 357-36
17. Caro CQ Fitz-Garald JM, Schroter RC. Atheroma and arterial wall shear:observation, correlation and proposal of a shear dependant mass transfermechanism for atherogenesis. Proceeding of the Royal Society of London B,1971, 177: 109-159.
18. Ku DN, Giddens DP, Zarins CK, et al. Pulsatile flow and atherosclerosis in the human carotidbifurcation. Arteriosclerosis, 1985, 5(3): 293-302.
19. 丁祖荣,王克强.人颈动脉分叉的 TF-AHCB模型.上海交通大学学报,2002, 36 (1):87-90.
20. Rosfors S, Stem SH, Rerstin JU, et al. Relationship between intima-media thichness in the common carotid artery and atherosclerosis in the carotid bifurcation. Stroke,1998, 29(7):1378-1382
21. PredimanK Shah, MD. New insights into the pathogenesis and prevention of acute coronary syndromes Am J Cardiol, 1997; 79(12B):17-23.
22. Davies MJ, Richardson PD, Woolf N, et al. Risk of thrombosis in humanatherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content.Br Heart J, 1993;69:377-381.
23. Howard M .Loree. Deffects of fibrous cap thickness on peak circumferential stress in model atherosclerotic.Circ Res, 1992;71:850-858.
24. Erling Falk, Prediman K-shah, Valentintion. Cormary plaque disruption.Circulation, 1995;92:657-671.
25. Servoss SJ, Jannzzi JL, Muller JE. Triggers of acute coronary syndromes. Prog Cardiovasc Dis, 2002,44:369-380
26. Fourcelot L, Tranquart F, Bray JM, et al. Ultrasound characterization and quantification of carotid atherosclerosis lesions. Minerva Cardioangiol, 1999, 47(I): 15-24
27. Polark JF, Shemanski L, O'Leary DH, et al. Hypoechoic plaque at US of the carotid artery :an independent risk factor for incident stroke in adults aged 65 years or older. Radiology 1998, 208:
649-654
28. Lee DJ, Sigel B,Swami UK, et al. Determination of carotid plaque risk by ultrasonic tissue characterization. Ultrasound Med Biol, 1998,24(9): 1291-1299
29. Joakimsen O, Bonaa KH, Stensland-Bugge E. Reproducibility of ultrasound assessment of carotid plaque occurrence, thickness, and morphology: the Tromoso Study. Stroke, 1997,28:2201-2207
30. Bluth E. Evaluation and characterization of carotid plaque. Seminars in Ultrasoud, CT,MRI. 1977.18:57-65
31. Aburahma AF, Kyer PD 3rd, Robinson PA, et al. The correlation of ultrasonic carotid plaque morphology and carotid plaque hemorrhage:clinical implication. Surgery, 1998,124(4):721-728
32. Gronhddt ML. Ultrasoud and lipoproteins as predictors of lipid-rich, rupture-prone plaques in the carotid artery. Aterioscler Thromb Vasc Biol, 1999,19:2-13
33. Gronhddt ML. Ultrasoud and lipoproteins as predictors of lipid-rich, rupture-prone plaques in the carotid artery. Aterioscler Thromb Vasc Biol, 1999,19:2-13
34. Gronholdt ML. Ultrasound and lipoproteins as predictors of lipid-rich ,rupture-prone plaques in the carotid artery. Arterioscler Thromb Vasc Biol,1999,19(1):2
35. North American Symptomatic Carotid Endaterectomy Trail Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis .N Eeg J Med, 1991, 325:445-453
36. European Carotid Surgery Trailists’ Collabrative Group. MRC European Carotid Surgery Trial. European Carotid Surgery Trial :Interim results for symptomatic patients with severe(70-99%) or with mild (0-29%) carotid stenosis Lancet,1991,377:1235-1243
37. Larry BG, Robert A, Kyra B,et al. Primary prevention of ischemic stroke. A statement for healthcare professional from the stroke council of American Heart Association. Stroke, 2001,32:280-299
38. Thomas J Tegos, Evi Kalodiki, Stella-Styliani Daskalopulou, et al. Stroke: epidemiology, clinical picture, and risk factors part ⅠofⅢ .Angiology,2000,51:793
39. William J,Zwiebel. Introduction to vascular ultrasonography .M.4th edition.US: W B Saunders Company,200.54-65
40. Tang L, Wang XG, Wu LW, et al. To evaluate the intracerebral correlation formation with CDFI in carotid stenosis patients. Chin J Med Imaging Technol,2002,18(3):229-230
41. 郑 宇,华 扬,凌 晨等. 颈动脉严重狭窄或闭塞对颅内循环的影响.中国医学影像技术.2004,20(6):901-90
1. 时晶,田金洲,王永炎等.血瘀证的生物学基础研究.中华中医药杂志,2006,21(6):363-364
2. Zhang X,Chirstenson LK, Nothnick WB,Regulation of MMP-9 expression and activity in the mouse uterus by estrogen. Mol Reprod Dev,2007,74(3):321-331
3. Gomez DE, Alonao DF, Yoshiji H, et al. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol, 1997, 74(2): 111-122
4. Yeh ET. High-sensitivity C-reactive protein as a risk assessment tool for cardiovascular disease. Clin Cardiol,2005,28(9):408-412
5. 田金洲,韩明向,涂晋文,杨承芝,杨惠民,邹忆怀,刘峘.《血管性痴呆的诊断、辨证及疗效评价标准》.北京中医大学学报,2001,23(5):24-30.
6. Georges Bellon ,Laurent Martiny,Arnaud Robinet. Matrix metalloproteinases and matrikines in angiogenesis. Critical Reviews in Oncology/Hematology 49 2004,49: 203–220
7. Lemaitre V, Amiento JD. Matrix metalloproteinase in development and disease.Birth Defects Res C Embryo Today,2006,37(7):1731-1736
8. Aguilera CM,George SJ, Johnson JL,et al. Relationship between type Ⅳ collagen degradation, a metalloproteinase activity and smooth muscle cell migriation and proliferation in cultured human saphenous vein. Cardiovasc Res,2003,58(3):679-688
9. Uglow EB,Slater S, Sala-Newby GB, et al. Dismantling of cadherin-mediated cell-cell contacts modulates smooth muscle cell proliferation.Circ Res.2003,92(12):1314-1321
10. Loftus J,Naylor R,goodall S, et al. Increased matrix metalloproteinase-9 activity in unstable carotid plaques. A potential role in acute plaque disruption.Stroke,2000,31:40-47
11. Heo JH,Kim SH, Lee KY, et al. Increase in plasma matrix metalloproteinase-9 in acute stroke patients with thrombolysis failure. Stroke,2003,34(6):e48-50
12. Keith Brew ,Deendayal Dinakarpandian , Hideaki Nagase. Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochimica et Biophysica Acta 2000,1477: 267~283
13. Rouis M,Adamy C,Duverger N,et al. Adenovious-mediated overexpression of tissue inhibitor of metalloproteinase-1 reduces atherosclerotic lesions in apolipoprotein E-deficient mice.Circulation,1999,100(5):533-540
14. Gospodarovvicz D,et al. Fgf proc natl acad sci USA,1984,81:6963-6967
15. 陈灏珠,杨昌生.动脉粥样硬化.见:陈灏珠主编.实用内科学,第十二版.北京:人民卫生出版社,2004:1459-1467
16. 王素菊 ,曹景敏.碱性成纤维细胞生长因子(bFGF) 的生物学特性研究进展.医学信息,1999,12(8):46-47
17. Lagrand WK,Visser CA,Hermens WT,et al. C-protein as acardiovascular risk factor:more than an epiphenomenona.Circulation,1999,100:96-102
18. Zwaka T P,Hombach V, Torzewski j, C-reactive protein mediated low density lipoprotein uptake by macrophages:implicatiONS for atherosclerotis.Circulation, 2001, 103(9): 1194-1197
19. Torzewski J, Torzewski M,Bowyer DE,et al.C-reactive protein frequently colocalizes with the interminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries.Arteroscler Thromb Vasc Biol 1998,18:1386-1392
20. Torze wski J,Tovzewski M,Bowyer DE,et al. C-reactive protein freguently colocalizes with the terminal complement complex in the inti-ma of early atherosclerotic cessions of human coronary arteries. .Arteriosder Thromb Vasc Biol,1998,18(9):1386-1392
21. Ridker PM.Inflammatory, statins, and the risk of stroke.Cracking a clinical conundrun.circulation, 2002,105:2583-2585
22. The Scandinavian Simvastatin Survival Study Group.Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease:the Scandinavian Simvastatin Survival Study(4S).Lancet,1994,344:1383-1389
23. Lemiengre I,Van DrielI,Chevalier P,et al.New analyses of Heart Protection Study.Lancet,2004,363:757-767
24. Plehn JF,Davis BR,Sacks FM,et al.Reduction of stroke incidence after myocardial infarction with pravastatin:the Cholesterol and Recurrent Events(CARE) Study.The CARE Investigators.Circulation,1999,99:216-223
25. Sato A,Asakura Y,YokotaC,et al.Lipoprotein disorder in brain infarction and hemorrhage.Int J Clin Lab Res,1998,28:39-46
26. Sridharan R.Risk factors for ischemic stroke:a case control analysis.Neuroepidemiology,1992,11:24-30
27. Jurgen G,Taddei-Peters WC,Koltringer P,et al.Lipoprotein(a) serum concentration and apolipoprotein(a) phenotype correlate with severity and presence of ischemic cerebrovascular disease.Stroke,1995,26:1841-1848
28. 朱爱华.炎症反应与急性脑梗塞血瘀证的相关性研究.北京中医药大学博士研究生论文.2007
29. 倪敬年.脑梗塞患者血瘀证与颈动脉粥样硬化的相关性研究.北京中医药大学硕士研究生论文.2007
30. 李林森,田金洲,蔡艺灵等.204例急性脑梗死患者血脂变化与痰证的相关性探讨.北京中医,2007,26(11):710-712
1. 陈灏珠,杨昌生.动脉粥样硬化.见:陈灏珠主编.实用内科学,第十二版.北京:人民卫生出版社,2004:1459-1467
2. Ross R.Glomset JA.The pathogensis of atherosclerosis (second of two parts) [J]N Engl J Med,1976,295(8):420-425
3. Ross R.Atherosclerosis:current understanding of mechanisms and future strategies in therapy [J]Transplant Proc,1993,25(2):2041-2043
4. Furchgott RF,Zawadzki JV.The obligatory role of endothelial Cells in the relaxation of arterial smooth muscle by acetylcholine.[J]Nature,1980;288(270):373
5. Palmer RM,Ferrige AG,Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor[J]Nature,1987,327(6122):524
6. Vaabdrager AB,Jonge HR.Signalling by cGMP2 –dependent protein kinase [J]Mol Cell Biochem,1996,157(12):23-30
7. Tedgui A ,Mallat Z.Anti-inflammatory mechanisms in the vascularwall [J]CircRes,2001,88:877-887
8. Harrison DG,Sayegh H,Ohara Y,etal. Regulation of expression of the endothelial cell nitric oxide synthase[J]Clin Exp Pharmacol Physiol,1996,23(3):251
9. Forstermann U,Kleinert H. Nitric oxide synthase: expression and expressional control of the three isoforms[J] Naunyn Schmiedebergs Arch Pharmacol,1995,352(4):351
10. Boger RH,BodeBoger SM,Brandes RP,etal. Dietary L-arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits: comparison with lovastatin [J]Circulation,1997,96(4):1282
11. Yanagisawa M,Kurihara H,Kimura S,etal. A novel potent vasoconstrictor peptide produced by vascular endothelial cells[J]Nature,1988,332(6163):411
12. Kinlay S,Behrendt D,Wainstain M,etal.The role of endothelin-1 in the constriction of human atheroscleroyic coronaryateries[J]Circulation,2001,104(3):1114-1118
13. Cody RJ. The potential role of endothelin as a vasoconstrictor substance in congestive heart failure[J]Eur Heart J,1992,13(11):1573
14. Jones GT,vanRij AM,Solomon C,etal. Endothelin-1 is increased overlying atherosclerotic plaques in human arteries[J]Atherosclerosis,1996,124(1):25
15. Warner TD,Klemm P. What turns on the endothelins?[J]InflammRes,1996,45(2):51
16. Cominacini L,Pasini AF,Garbin U,etal.Oxidized low density lipoprotein (ox LDL) binding to ox –LDL receptor-1 in endothelial cells induces the activation of NF-kappaB through an increasedproduction of intracellular reactive oxygen species[J]Biol Chem,2000,275:125633-125638
17. Donald ES,Steven DM,Christian S et al Cell,1988,52:925
18. Hwang SJ,Ballantyne CM,Sharrett AR. Circulating adhesion molecules VCAM-1,ICAM-1 and E-Selectinin carotid atherosclerosis and incident coronary heart disease cases: The atherosclerosis risk in communities(ARIC)study [J]Circulation,1997;96(12):4219-4225
19. Cybulsky ML,Fies JW,Williams A J etal. Gene structure,chromosomal location,and basis for alternative mRNA splicing of the human VCAM-1gene [J]Proc Natl Acad Sci,1991 Sep,88
20. (17):7859-63
21. OBrien KD,McDonald TO,Chait A etal.Neovascular expression of E-selectin, intercellular adhesion molecule-1,and vascular cell adhesion molecule2-1 in human atherosclerosis and their relation to intimal leukocyte content [J]Circulation,1996,93:672-682
22. Libby P,Sukhova G,Lee RT etal. Cytokines regulate vascular functions related to stability of the atherosclerotic plaque [J]Cardiovasc Pharmacol,1995,25(Suppl2):S9-12
23. Bevilacqua MP,et al[J]Clin Invest,1993;91(2):379
24. Shebuski RJ,Kilgore KS. Role of inflammatory mediators in thrombogenesis [J] Pharmacol ExpTher,2002;300(3):729-35
25. Martin T,Cardarelli PM,ParryGC,etal. Cytokine induction of monocyte chemoattractant protein-1 gene expression in human-endothelial cells depends on the cooperative action of NF-kappaB and AP-1[J] EurJ Immunol,1997,27(5):1091
26. Ross R..The pathogenesis of atherosclerosis:a perspective for the 1990s [J]Nature 1993,362: 801一809
27. Zeiher AM , Fisslthaler B, Schray-UtzB, etal. Nitric oxide modulates the expression of monocytechemoattractant protein1in cultured human endothelial cells[J] Circ Res,1995,76(6):980
28. Gerszten RE,Garcia-ZepedaEA,LimYC,etal. MCP-1 and IL-8 trigger firm adhesion of monocytes to vascular endothelium under flow conditions[J] Nature,1999,398(6729):718
29. Witztum JI,Steinberg D.Role of oxidized lowdensity lipoproteins in atherogenesis [J] J Clin Invest,1991,88:1785-1792
30. Steinberg D.Atherosclerosis,1997,131:5
31. Fleming I,Mohamed A,Galle J,et al.Oxidized low-density lipoprotein increase superoxide production by endothelial nitric oxide synthase by inhibiting PKCa [J] cardiovasc,2005,65 :897-906
32. Kawashima S,Yokoyama M. Dysfunction of Endothelial Nitric Oxide Synthase and Atherosclerosis [J] Arterioscler Thromb Vasc Biol,2004,24(6) :998-910
33. Luciana V,Stefan H,Franco R,et al. Effect of native and oxidized lowdensity lipoprotein on endothelial nitric oxide and superoxiede production [J] Circulation,2000,101:1261
34. Sawamura T,Kume N,Aoyama T,etal.An endothelial receptor for oxidized lowdensity lipoprotein[J] Nature,1997,386(6):73-76
35. Morawietz H,Rueckschloss U,Sawamura T,etal. Angiotensin induces LOX-1,the human endothelial receptor for oxidized low-density lipoprotein[J] Circulation,1999,100(9):899-902
36. Kume N,Murase T,Moriwak H,etal. Inducible expression of lectin-like oxidized LDL receptor-1 in vascular endothelial cells[J] CircRes,1998,83:322-325
37. Angnes G,vanVelzen RP,Silva D,etal.Characterization of a receptor for oxidized low-density lipoproteins on rat Kupffer cells:similarity to macrosialin[J] Biochem J,1997,322:411:415
38. Ling W,Lougheed M,Suzuki H,etal. Oxidized or acetylated low density lipoproteins are rapidly cleared by the liver in mice with disruption of the scavenger receptor class A typeI//II gene [J] Clin Invest,1997,100:244-252
39. Acton SL,Scherer PE,Lodish HF,etal. Expression cloning of SR-BI a CD36-related classB scavenger receptor[J] Jbiol Chem,1994,269(33):21003-21009
40. Acton S,etal. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor[J] Science,1996,271:518-520
41. Pearson A,etal.Expression cloning of dSR-CI,a classC macrophage-specific scavenger receptor from drosophila melanogaster[J] Proc Natl Acad Sci U.S.A.1995,92:4056-4060
42. Bobik A,Agrotis A,Kanellakis P,etal. Distinct patterns of transforming growth factor beta isoform and receptor expression in human atherosclerotic lesions:Colocalization implicates TGF- beta in fibrfatty lesion development [J]Circulation,1999,2883 -2891
43. Li D,Mehta JL.Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of onocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells [J]Circulation,2000,275:12633-12638
44. Ferrara M, Henael WJ.Pituitary follicular cells secrete a novel heparin binding growth factor specific for vascular endothelial cells[J] Biochem Biophys Res Commun,1989,161( 2) :851
45. Pettersson A,bhgy JA, Brown LF,et al. Heterogeneity of angiogenic respones induced in different normal adult tissues by vascular permeability factor/ vascular endothelial growth factor [J] Lab Invest,2000,80 (1):99
46. Neschis DG,Sfford SD,Hanna AK,etal. Antisense Basic fibroblast growth factor gene transfer reduces early intimal thickening in a rabbit femoral artery balloon injury model[J] Vasc Surg,1998,27:126-134.
47. De Larco JE,Todaro GJ.Growth factors from murine sarcoma virustransformed cells [J] Proc Natl Acad Sci USA, 1978;75(8):4001-4005
48. Mallat Z,Gojova A,Marchiol-Fournigault C, et al. Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice[J] Circ Res,2001, 89(10):930-934
49. Argmann CA,Van Den Diepstraten CH,Sawyez CG,et al. Transforming growth factor-β1 inhibits macrophage cholesterol ester accumulation induced by native and ox-idized VLDL remnants[J] Arterioscler Throm Vasc Biol, 2001, 21(12):2011-2018
50. Zuckerman SH,Panousis C, Evans G.TGF-beta reduced hinding of high-density lipoproteins in murine macrophages and macrophage-derived foam cells[J] Atherosclerosis, 2001,155(1):79-85
51. Minami M, Kume N, Kataoka H, et al. Transforming growth factor-beta(1)increases theexpression of lectin-like oxidized low-density lipoprotein receptor-1[J] Biochem Biophys Res Commun, 2000,272 (2):357-361
52. Oemar BS, Werner A, Gamier JM, et al. Human connective tissue growth factors expressedin advanced atherosclerotic lesions[J] Circulation 1997, 95(4):831-839
53. Siebenlist U,Franzoso G, Brown K. Structure,regulation and function of NF-kappa B[J] Annu Rev Cell Biol,1994,10:405
54. Ricote M,Li AC,Willson TM,etal. The peroxisome proliferator activated receptor-gamma is a negative regulator of macrophage activation[J]Nature,1998,391:79-82.
55. Viita H,Yla Herttuala S. Effects of lipoxygenases on gene expression in mammalian cells.In Sen CK,Sies H,BaeuerlePAeds. A NTIOXIDANT and redox regulation of genes.San Diego Academic Press,2000,339-358
56. Gerszten RE,Mach F,Sauty A,etal.Chemokines leu kocvtes and atherosclerosis[J] Lab Clin Med,2000,136:87-92
57. Marx N,Bourcier T,Sukhova GK,etal. PPAR gamma activation in human endothelial cells increases plasminogen activator inhibitor type 1 expression :PPAR Gamma as a potential mediator in vascular disease.[J]Arterioscler Thromb Vasc Biol,1999,19:546-551
58. Mallat Z,Benamer H,HugelB,etal. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation,2000,101:841-84
1. 中国中西医结合研究会第一次全国活血化瘀学术会议订.血瘀证诊断试行标准.中西医结合杂志,1983,3(3):封二
2. 第二届全国活血化瘀研究学术会议修订.血瘀证诊断标准.中西医结合杂志,1987,7(3):129
3. 王阶,陈可冀,翁维良等.血瘀证诊断标准的研究.中西医结合杂志,1988,8(10):585
4. 寺泽捷年.瘀血证的证候诊断刍议.国外医学中医中药分册,1984,(1):1
5. 血瘀证研究国际会议.血瘀证诊断参考标准.实用中西医结合杂志,1989,2(1):7
6. 小川新.国际瘀血证诊断标准草案.第一届中日血瘀证综合研究会议论文摘要,1992,4
7. 葛金文等,自身免疫病血瘀证患者自由基损伤的研究,湖南中医学院学报 1994;14(3):47
8. 谢林等,丹紫康膝冲剂对膝关节退行性骨关节病患者氧自由基代谢的影响,中国中医骨伤科 1996;4(2):8
9. 王仁秀等,血瘀型心脑血管疾病舌诊之初探,微循环学杂志 1995;5(1):37
10. 张道杰等,血瘀证患者血浆组织型纤溶酶原激活物及其抑制物的变化,解放军医学高等专科学校学报 1999;27(2):114
11. 吴双虎等,氧自由基对血瘀证患者微循环影响的临床研究,中国中西医结合外科杂志 1999;5(5):287
12. 倪瑾等,寒凝血瘀证与血液流变学观察意义,辽宁中医杂志 1996;23(12):568
13. 童家罗,60例型糖尿病血瘀证观察分析,山东中医杂志 1999;18(8):350
14. 李晓明等,肾脏病血瘀证患者血浆内皮素a颗粒膜蛋白140 含量测定的意义,中国中医基础医学杂志,1996;2(5):35
15. 蔡钦朝等,血瘀证患者血管内皮内分泌功能的观察,安徽中医学院学报 1998;17(2):61
16. 陈云波等,血瘀证兔模型血管内皮细胞培养的形态结构改变初探,中国中医基础医学杂志 1999;5(5):12
17. 廖福龙,老年血液流变学改变及与中医血瘀证的关系,老年医学与保健 1998;4(4):4
18. 马治中等.老年大鼠血液流变学参数的变化,北京医科大学学报 1996;28(6):450
19. 蔡辉等,老年血瘀证症患者甲襞微循环的观察,微循环技术杂志 1997;5(1):42
20. 王忠等,后基因组时代中医证候组学研究的思考,中国中西医结合杂志 2001;21(8):621
21. 李静等,血管通对实验性动脉粥样硬化家兔血管壁血小板衍化生长因子 A、B及 c-myc基因表达的影响,中国中西医结合杂志 1995;15(1):33
22. 郭蕾、王永炎、张志斌,关于证候概念的诠释,北京中医药大学学报 2003;26(2):5-8