摘要
目的：观察降脂消斑片对冠心病心绞痛痰热血瘀证的临床疗效及从其对鹌鹑高脂血症及AS模型的实验研究,来探讨其作用机理。
方法：1.选择2009年7月至2010年7月在湖南中医药大学第一附属医院心血管内科住院及门诊治疗的60例冠心病心绞痛痰热血瘀证患者,采用随机的原则分为两组,即治疗组和对照组,分别给予西医基础治疗加降脂消斑片或脂降宁片,观察8周,观察治疗前后中医证候、心绞痛、心电图及硝酸甘油停减率的变化,并对TC、TG、LDL-C、HDL-C、ApoA1、ApoB、hs-CRP、IL-6等指标进行比较。
2.120只鹌鹑,随机分为正常组(20只)和造模组(100只),运用单纯高脂饲料喂养7周后抽样示成功造成鹌鹑AS模型,随机分为：正常组,模型对照组,脂降宁片组,降脂消斑片高(1.56 g/kg)、中(0.78g/kg)、低(0.39 g/kg)剂量组。观察指标包括TC、TG、LDL-C、HDL-C、Leptin、PLA2、ApoA、ApoB、CRP、TNF-α、IL-6、主动脉及冠状动脉内膜AS斑块情况。
结果：1.中医证候改善率治疗组为90.00%,对照组为83.33%,两组比较差异有统计学意义(P<0.05)。心绞痛疗效、心电图疗效总有效率、硝酸甘油停减率治疗组分别为86.67%、73.33%、86.67%,对照组分别为76.67%、53.33%、70.00%,两组比较,差异均有统计学意义(P<0.05)。治疗后治疗组TC、TG、HDL-C、LDL-C、ApoA1、ApoB、hs-CRP、TNF-α与IL-6等指标与对照组比较,差异有统计学意义(P<0.01或P<0.05)。
2.降脂消斑片能明显降低鹌鹑高脂血症及AS模型血清TC、TG、LDL-C及Leptin、PLA2含量(P<0.01或P<0.05),并可升高血清ApoA、降低血清Apo-B、使ApoA/ApoB比值提高(P<0.01或P<0.05)；降脂消斑片高、中剂量组可降低血清CRP、TNF-α与IL-6水平(P<0.01或P<0.05)；能明显减少主、冠状动脉内膜粥样斑块形成,其作用随剂量、给药时间增加而增强(P<0.01或P<0.05)。
结论：降脂消斑片具有较强调节血脂及治疗AS作用,其作用机理与其参与调节血脂、脂蛋白、减轻病变过程中的血管内膜炎症反应等有关。
Objective:To observe the therapeutic effects of Jiang Zhi Xiao Ban Pill(JZXBP) on patients with angina pectoris caused by phlegm-heat and blood Stasis and experimental research in quail with atherosclerosis and hyperlipidemia model to explore its potential pharmacological mechanism.
Methods:1. To select 60 eligible inpatients, who has angina pectoris caused by phlegm-heat and blood Stasis, and they all have been treated by the cardiovascular medicine department and outpatients, the 1st hospital affiliated to Hunan university of TCM, from July 2009 to July 2010. Then divide them into two groups randomly, the ZhiJiangNing pill controlled group (A)and the group treated by JZXBP(B). After 8 weeks treatment, observe the changes of syndromes, angina pectoris, ECG and the rate of nonused or decreased Nitroglycerin, as well as the indexes such as TC, TG,LDL-C, HDL-C,ApoA1, ApoB,hs-CRP,TNF-αand IL-6. 2.120 quails were randomly divided into normal group(20) and high lipid group(100).Models of hyperlipidemia and atherosclerosis in quails was built with high cholesterol diet in 7 weeks. They were randomly divided into 6 groups:normal group,high lipid group, Simvastatin group,Zhi Jiang Ning Pill group,JZXBP 0.39 g/kg group,JZXBP 0.78 g/kg group, JZXBP 1.56g/kg group.The levels of plasma total cholesterol (TC), triglyceride (TG),low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol(HDL-C), apolipoprotein A(ApoA) and apolipoprotein B (ApoB),Leptin,PLA2,C reactive protein(CRP),TNF-a, IL-6,changes of the atherosclerotic plaque of aorta and coronary artery were observed.
Results:1. The mended rate of syndrome in group B is 90.00%, while 83.33% in group A. There has statistical differences between the two groups(P<0.05). The total effective rates of curative effects of angina pectoris,ECG,decreases in the dose of Nitroglycerinin group B are 86.67%,73.33% and 86.67% respectively,while76.67%,53.33% and 70. 00% in group A respectively.They both have significant differences between the two groups(P<0.05).While the indexes such as TC,TG, LDL-C,HDL-C,ApoA1,ApoB,hs-CRP,TNP-αand IL-6 in group B compar-ed with group A, the differences is significant (P<0.05 or P<0.01).
2.JZXBP group had remarkable decreases in the level of serum TC,TG,LDL-C,ApoB,Leptin,PLA2, (P<0.05 or P<0.01), and increases in the level of serum ApoA and ApoA/ApoB (P<0.05 or P<0.01). JZXBP 0.78 g/kg,1.56 g/kg group could evidently lower the level of serum CRP, TNF-αand IL-6 (P<0.05 or P<0.01).The number of atherosclerotic plaques of aorta and coronary artery,were significantly less in the JZXBP pill than that in the model group (P<0.05),what correlates with its dose and period of treatment (P<0.01 or P<0.05).
Conclusion:JZXBP could play a stronger role in regulating blood lipid and decelerating the progression of atherosclerosis and eliminating (or stabilize) atherosclerotic lipid plaque,probably by decreasing the levels of CRP,TNF-αand IL-6 in tandem inhibiting inflammatory reaction in endangium and regulating lipometabolism and the abnormality of blood lipid.
引文
[1]Cardiovascular diseases (CVDs). WHO web site.Available at: http://www.who.int/mediacentre/factsheets/fs317/en/index.html Accessed May 15, 2011.
[2]陈在嘉,高润霖.冠心病[M].人民卫生出版社,2002：685.
[3]Lusis AJ.Atherosclerosis[J].Nature,2000,407:233-241.
[4]Libby P.Inflammation in atherosclerosis[J].Nature,2002,420:868-874.
[5]Young JL,Libby P,Schonbeck U.Cytokines in the pathogenesis of atherosclerosis[J]. Thromb Haemost,2002,88:554-567.
[6]Izzo JL.The role of the renin-angiotensin system in vascular health:use of ACE inhibition to improve vascular function[J]. Heart Dis,2000,2:380-383.
[7]Bottiger LE,Carlson LA,Ekelund LG, et al.Raised erythrocyte sedimentationrate in asymptomatic hyperlipidaemia[J]. BMJ,1973,2:681-684.
[8]Pairs D,Town T,Humphrey J,et al.Cholesterol modulates vascular reactivity to endothelin-1 by stimulatina proinflammatory pathway[J].Biochen Biophys Res Com-mun.2000,274:553-558.
[9]Ferroni P,Basili S,Vieri M,et al.Soluble P-selection and proinflammatory cytokines in patients with polygenic type Ⅱa hypercholesterolemia[J].Haemostasis.1999,29:277-285.
[10]DaviT,GreseleP,VioliF,etal.Diabetes mellitus,hypercholesterolemia,and hyperten-sion but not vascular disease per se are associated with persistent platelet activation in vivo:evidence derived from the study of peripheral arterial disease[J].Circulation. 1997,96:69-75.
[11]Dickfeld T,Lengyel E,May AE.et al.Trasient interaction of activated platelets with endothelial cells induces expression of monocytechemoattractant protein-1 via a p38 mitogen-activated protein kinase mediated pathway-Implications for atherogenesis[J]. Cardiovasc Res.2001,49:189-199.
[12]徐成斌.论急性冠脉综合征他汀类药物早期应用的益处[J].中华心血管杂志,2001,29(3)：129.
[13]吕以林,颜淑红,郭涛等.辛伐他汀对不同血脂水平急性冠状动脉综合征患者血清基质金属蛋白酶水平的影响[J].中华心血管病杂志,2004,32(2)：109-113.
[14]Zeng B;Prasan A,Fung KC,et al.Elevated circulating levels of matrix metallo pmteinase-9 and-2 in patients with symptomatic coronary artery disease[J].Intern Med J,2005,35(6):331-5.
[15]Pepys MB,Hirschfield GM.C-reactive protein:a critical update[J].J Clin Invest, 2003,111(12):1805-1812.
[16]李建军.C反应蛋白与冠心病的关系[J].心血管病学进展,1999,14(5)：319.
[17]石刚,刘婷.冠心病及其常见中医证型与超敏C反应蛋白的关系探讨[J].中医药临床杂志,2007,19(1)：29-30.
[18]郑刚.抗血管壁慢性炎症--动脉粥样硬化防治的新思路[J].中西结合心脑血管病杂志,2006,4(2)：143-146.
[19]王战坤,蔡巍,邵乐文,等.细胞因子与冠状动脉狭窄程度的相关性研究[J].中华心血管病杂志,2003,31(8)：588-590.
[20]Hoffmeisfer HM,Ehlers R, Buttcher E,et al.comparison of C-reactive protein and terminal complement complex in patients with Unstable angina pectoris versus stable angina pectoris[J].AM J Cardiol,2002,89:909-912.
[21]Pasceri V,Chang J,Willerson JT,et al.Modulation of C-reactive protein mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs[J].Circulation,2001,103:2531-2534.
[22]Burke A P,Tracy R P,Kolodgie F,et al.Elevated C-reactive protein values and atherosclerosis in sudden coronary death:association with different pathologies[J]. Circulation,2002,105:2019-2023.
[23]Takeyla N,William S,Cecelia X,et al.C-reactive protein stimulates MMP-1 expression in U937 histiocytes through FCRII and extracellular signal-regulated kinasepathway [J]. Arter Throm Vascular Biol,2004,24:61-66.
[24]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.慢性稳定性心绞痛诊断与治疗指南[J].中华心血管病杂志,2007,35(3)：195-206.
[25]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.不稳定性心绞痛和非ST段抬高心肌梗死诊断与治疗指南[J].中华心血管病杂志,2007,35(4)：295-304.
[26]郑筱萸主编.中药新药临床研究指导原则(试行)[M].北京：中国医药科技出版社,2002：68-73,383-385.
[27]王永炎主编.中医内科学[M].上海科学技术出版社,1997：123.
[28]朱文锋.中医诊断学(第六版)[M].上海.上海科学技术出版社.2000：141-145.
[29]杨永宗.中国动脉粥样硬化病理生理学研究进展[J].中国动脉硬化杂,2004,12(4)：481-489.
[30]田卉,李丽艳,马建慧,等.鹌鹑实验性动脉粥样硬化治疗模型的建立[J].石河子大学学报(自然科学版),2005,23(4)：425-427.
[31]宋洪涛,郭涛.中药红曲对高脂血症鹌鹑模型的降血脂作用[J].中草药,1998,29(5)：317-319.
[32]张均田.现代药理实验方法(下册)[M].北京医科大学中国协合医科大学联合出版社，1998：1266-1267.
[33]陈灏珠.实用内科学(第12版)[M].人民卫生出版社,2005：1077.
[34]叶任高,陆再英.内科学(第6版)[M].人民卫生出版社,2004：821.
[35]王吉耀.内科学[M].人民卫生出版社,2005,8：1019.
[36]Yamashita H,Ehara S,Yoshiyama M,et al.Elevated plasma levels of oxidized low density lipoprotein relate to the presence of angiographically detected complex and thrombotic coronary artery lesion morphology in patients with unstable angina[J].Circ J,2007,71 (5):681-687.
[37]Amit V. Khera, M.D.,Marina Cuchel, M.D.,Ph.D,Margarita de la Llera-Moya,Ph D.,et al.Cholesterol Efflux Capacity,High-DensityLipoprotein Function,and Atherosc-lerosis[J].New Engl J Med,2011,364:127-35.
[38]Jay Heinecke,M.D..HDL and Cardiovascular-Disease Risk—Time for a New Approach?[J]. New Engl J Med,2011,364:170-171.
[39]王劲松,余金明.普罗布考可改善心血管病高风险人群冠状动脉事件结局[J].中国动脉硬化杂志,2008,16(10)：763-765.
[40]Mike Mitka.CETP Inhibition Shows Promise as Way to Reduce Cardiovascular Disease Risk[J].JAMA,2011,305(2):136-137.
[41]中国成人血脂异常防治指南制订联合委员会.中国成人血脂异常防治指南[J].中华心血管病杂志,2007,35(5)：3902-4131.
[42]钱卫冲,杜福昌,王海燕,等.江苏省心血管病流行病学研究回顾[J].中华心血管病杂志,2008,36：110-112.
[43]刘静,赵冬,吴兆苏,等.低密度脂蛋白胆固醇与心血管病发病关系的前瞻性研究[J].中华心血管病杂志,2001,29(9)：561-565.
[44]李莹,陈志红,周北凡,等.血脂和脂蛋白水平对我国中年人群缺血性心血管病事件的预测作用[J].中华心血管病杂志,2004,32(7)：643-647.
[45]赵文华,张坚,由悦,等.中国18岁及以上人群血脂异常流行特点研究[J].中华预防医学杂志,2005,39(5)：306-310.
[46]吴兆苏,姚崇华,赵冬,等.11省市队列人群心血管病发病前瞻性研究Ⅱ个体危险因素聚集与心血管病发病的关系[J].中华心血管病杂志,2001,29(4)：246-250.
[47]国家九五科技攻关课题协作组.我国中年人群心血管病主要危险因素流行现状及从80年代初至90年代末的变化趋势[J].中华心血管病杂志,2001,29(2)：74-79.
[48]吴桂贤,吴兆苏,王薇,等.1992-2002年北京一组队列人群心血管病危险因素变化趋势研究[J].中华心血管病杂志,2005,33(8)：748-753.
[49]王齐齐,刘紫燕,史明娟,等.近6年冠心病患者危险因素变化调查[J].心脑血管病防治,2008,8(1)：24-26.
[50]关绍晨,汤哲,吴晓光,等.北京城乡老年人群代谢综合征的现状调查[J]中华老年医学杂志,2006,25：219-221.[]陈涛,李卫,胡泊,等.北京地区城乡居民代谢综合征及其组分患病率对比研究[J].中国糖尿病杂志,2009,17(12)：902-904.
[51]成守金,罗云杰,周桂梅.中老年高级知识分子3428名1998～2004年心血管病危险因素水平及聚集程度分析[J].2005,9(3)：11-13.
[52]国家“九五”科技攻关课题协作组.我国中年人群心血管病主要危险因素流行现状及从80年代初至90年代末的变化趋势[J].中华心血管病杂志,2001,29(2)：74-79.
[53]李莹.中国心血管病危险因素流行状况[J].当代心脏病学进展,2007：523-526.
[54]王薇,赵冬,吴兆苏,等.中国11省市35-64岁人群血清甘油三酯分布特点及与其他心血管病危险因素关系的研究[J].中华流行病学杂志,2001,22(1)：26-29.
[55]Rosenson RS,Tangney CC.Antiatherothromboic properties of stains-Implications for cardiovascular event reduction[J]. JAMA,1998,279:1643-1650.
[56]Pedersen TR,Faergeman O,Kastelein JJP,et al.The Incremental Decrease in Events through Aggressive Lipid Lowering (IDEAL) Study Group-High dose atorvastatin vs usual dose simvastatin for secondary prevention after myocardial infarction-The IDEAL study:a randomized controlled trial[J].JAMA.2005,294:2437-2445.
[57]LaRosa JC,Grundy SM,Waters DD,et al.Treating to New Targets (TNT) Investig-ators-Intensive lowering with atorvastatin in patients with stable coronary disease[J]. N Engl J Med.2005,352:1425-1435.
[58]庞晓军.治疗高脂血症药物的合理应用[J].中华临床医药,2003,4(12)：114-115.
[59]中华医学会心血管病学分会,中华心血管病杂志编辑委员会.正确认识合理使用调脂药物[J]：中华心血管病杂志,2001,29(12)：705-706.
[60]Zhang Y,Proenca R,Maffei M,et al.Positional cloninng of the mouse obese gene and its human homologue[J].Nature,1994,372:425-432.
[61]Halas JL,Gajiwala KS,Maffei M,et al.Weight-reducing effects of the plasma protein encoded by the obese gene[J].Science,1995,269:543-546.
[62]王艳梅,郭贤利,刘生梅.瘦素在心血管疾病中的作用[J].陕西医学杂志,2008,37(3)：347-348.
[63]Campfied LA,Smith FJ, Guisez Y, et al.Recombinant mouse ob protein:evidence for a peripheral signal linking adiposity and central neural networks[J].Science,1995, 269:546-549.
[64]Jerzy KW.Response of Leptin to short-term and prolonged overfeeding in humans [J].Clin Endocrinol Metab,1996,81:4162-4166.
[65]Collins S,Kuhn GM,Petro AE,et al.Role of Leptia in fat regulation [J].Nature, 1996,380:677.
[66]Collins S,Surwit RS.Pharmacologic manipulation of ob expression in a diety model of obesity[J].Biol Chem,1996,271: 9437-9440.
[67]Caro JF,Sinba MK,Kolaczynski JW, et al.Leptin:the tale of an obesity gene[J]. Diabetes,1996,45:1455-1459.
[68]Bai Y,Zhang S,Kim KS,et al.Obese gene expression alters the abilty of 30 A5 preadipocytes to respond to bpogenic hormones[J].Biol Chem,1996,271:13939-13942.
[69]La Cava A,Alviggi C,Matarese GUnraveling the multiple roles of leptin in inflammation and autoimmunity[J].J Mol Med,2004,82(1):4-11.
[70]Chiu KC,Chu A,Chuang LM.et al.Association of leptin receptor polymorphism with insulin resistance[J].Eur J Endocrinol,2004,150(3):725-729.
[71]Schmidt MI,Duncan BB,Vigo A,et al.Leptin and incident type 2 diabetes:risk or protection?[J].Diabetologia,2006,49(5):2086-2096.
[72]Park HY, Kwon HM,Lira HJ,et al.Potential role of leptin in angiogenesis:leptin induces endothelial cell proliferstion and expression of matrix metalloproteinases in vivo and in vitro[J].Exp Mol Med,2001,33(2):95-102.
[73]Salopuro T,Pulkkinen L,Lindstrom J.Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight:the Finnish diabetes prevention study[J].Int J Obes,2005,29(6):1245-1251.
[74]Zhang Y,Scarpace PJ.The role of leptin in leptin resistance and obesity[J].Physiol Behav,2006,88(6):249-256.
[75]杨磊,孟庆雄.磷脂酶A2的研究进展[J].食品与药品,2007,9(7)：52-54.
[76]Six DA,Dennis EA.The expanding superfamily of phospholipase A2 enzymes: classification and characterization[J].Biechim Biophys Acta,2000,1488(1-2):1-19.
[77]Sanchez-Quasada JL,Benitez S,Ordonez-Llanos J.Electronegative low-density lipoprotein[J].Curr Opin Lipidol,2004,15:329-335.
[78]Benitez S,Benitez S,Villegas V, et al.Impaired hinding affinity of electrmlegative low-density lipoprotein(LDL) to the LDL receptor is related to nonesterifled fatty acids and lysophoPhatidyl-choline content[J].Biochemistry,2004,43:15863-15872.
[79]Caqenter KL,Denuis IF,Challis IR,et al.Inhibition of lipoprotein-associated phospholipase A2 dinlinislles the death-inducing effects of oxidised LDL on human monocyte macrophages[J].FEBSI,2001,505:357-363.
[80]唐建花,王卫淑,装志强,等.脂蛋白相关磷脂酶A2浓度与兔动脉粥样硬化关系的研究[J].中国药物与临床,2009,9(2)：108-110.
[81]Macphee CH.Lipoprotein-associated phospholipase A2:a potential new risk factor for coronary artery disease and a therapeutic target [J].Curr Opin Pharmacol,2001,1: 121-125.
[82]陈江天,陈红,任景怡,等.瑞舒他汀和阿托伐他汀对高胆固醇血症患者血浆脂蛋白相关性磷脂酶A2的影响[J].中国综合临床,2008,24(4)：359-362.
[83]Esper RJ,vilarino JO,Machado RA,et al.Endothelial dysfunction in normal and abnormal glucose metabolism[J].Adv Cardiol,2008,45:17-43.
[84]Ross R.The pathogenesis of atherosclerosis a perspective for the 1990s[J]. Nature, 1993,326:801.
[85]Amento EP, Ehssi N, Palmer H, et al. Cytokines and growthe factors positively and negatively regulate interstitial collagen gene expression in human vascular Smooth muscle cells [J].Arterrioscler Thromb,1991,11:1223-1230.
[86]Calis ZS,Muszynski M,Sukhova, el al.Enbanced expression of vascular matrix metallo proteinases induced in vitro by cytokines and in region of human atherosclerotic lesions[J].Ann NY Acad Sci,1995,748:501-507.
[87]Mulvihill NT,Foley JB.Inflammation in acute coronary syndromes [J].Heart,2002, 87:201-204.
[88]Kinlay S,Andrew P.Inflammation,the endothelium and the acute coronary syndromes[J]. J Cardiovasc Pharmacol,1998,32:62-66.
[89]李嘉强译.炎性标志物与冠心病[J].心血管病学进展,2003,24(3)：235.
[90]肖黎保,李伟,卢开林,等.C反应蛋白与冠心病的关系[J].中西结合心脑血管病杂志,2009,7(7)：816-817.
[91]赵坤元,赵惠.李七一论治高脂血症经验[J].上海中医药杂志,2006,40(3)：24-25.
[92]杨胜兰.高脂血症的基本病机探讨[J].中医杂志,2005,46(11)：861-863.
[93]龚一萍,王幸儿.高脂血症与心脉相关性探讨[J].北京中医药大学学报,2002,25(1)：62-63.
[94]孙天福,马仁生.袁海波教授治疗高脂血症学术思想及经验[J].中医研 究,2004,17(2)：41-44.
[95]于文涛,田元祥.杨牧祥教授从痰瘀论治高脂血症的经验[J].河北中医,2006,28(3)：165-166.
[96]杨瑞合.肾虚与高脂血症关系的探讨[J].中西医结合杂志,1989,9(5)：313.
[97]董和,肖佐桃,吴子明.补肾降脂药物作用的观察[J].中西医结合杂志,1991,11(1)：25-27.
[98]刘仁人,陈少维,陆金宝,等.固本降脂丸治疗中、老年高脂蛋白血症临床观原发性高脂血症的中医证候规律研究察[J].上海中医药杂志,1995,(10)：26-27.
[99]张昌文.血脂异常的中医病机与治疗[J].新中医,2008,40(1)：3-4.
[100]杨学武.浅谈高脂血症的辨证论治[J].河南中医,2007,27(9)：81-82.
[101]刘宗莲,徐淑文.陈鼎祺辨治高脂血症经验[J].中医杂志,2002,43(5)：336-337.
[102]杨坚毅.老年高脂血症辨治经验[J].中医杂志,2001,42(9)：529-530.
[103]杨学武.浅谈高脂血症的辨证论治[J].河南中医,2007,27(9)：81-82.
[104]雷义举.中医辨证治疗高脂血症82例[J].陕西中医,2002,23(6)：507-508.
[105]佟丽娟.高脂血症的病因病机及辨证分型治疗[J].中医药学刊,2002,20(2)：244.
[106]金玉龙,赵志新.降脂通脉冲剂对高粘、高脂血症患者血流变学及血脂影响的观察[J].中西医结合实用临床急救,1997,4(11)：449-501.
[107]徐承水.人参降血脂作用的实验研究[J].长春中医学院学报,2000,16(3)：45-46.
[108]赵莉敏,石建辉,赵国华,等.槐菊冲剂治疗高脂血症的临床研究[J].中国医药学报,1997,12(5)：30-31.
[109]张秋华,孙文静.益气活血方对大鼠的调节作用与NO水平的影响[J].中国实验方剂学杂志,2003,9(1)：19-21.
[110]王宇晖,周超凡,中药降脂研究进展[J],中国中药杂志,1999,24(3)：184.
[111]黄敬文,段剑飞,秦书芝.中药治疗高脂血症作用机理研究进展[J].中国现代实用医学杂志,2006,5(8)：30-31.
[112]贺圣文,刘同美,尤敏,等.马齿苋对家兔实验性高脂血症的防治作用[J].中草药,1997,28(4)：221-223.
[113]任世存,乔晓鸣.沙棘降脂胶囊对高脂血症大鼠脂代谢及血液流变学影响研究[J].江苏中医,2005,26(8)：52.
[114]何菊英,刘松青,决明子的药理作用及其临床应用[J].药学实践杂志,2001,19(2)：111.
[115]王新华,泽泻研究进展[J],中草药,1999,30(7)：557.
[116]李吉平,吕忠智,吕怡芳,等.西洋参茎叶皂甙对高脂血症大鼠脂蛋白、胆固醇代谢的影响及其抗氧化作用[J].中国药学杂志,1993,28(6)：355.
[117]罗琼,李瑾玮,张声华,等.枸杞及其多糖对家兔血脂的影响[J].食品科学,1997,18(4)：5.
[118]张洪,马红斌,蔡鸿生.降脂中药浅谈[J].时珍国药研究,1995,6(1)：34-35.
[119]刘萍,张静生.冠心康对高脂血症大鼠血脂影响的研究[J].中成药,2003,25(9)：757.
[120]王玉仙,马学荣.泽泻汤加味治疗高血脂症103例[J].陕西中医,2005,26(2)：8.
[121]梅全喜.现代中药药理与临床应用手册[M].中国中医药出版社,2008：618.
[122]罗琼,李瑾玮,张声华,等.枸杞及其多糖对家兔血脂的影响[J].食品科学,1997,18(4)：5.
[123]沈薇薇.山海经译注[M].黑龙江人民出版社,2002：13.
[124]王霞,凌世峰.虎杖药理作用研究进展[J].海军医学杂志,2004：25(2)：179-181.
[125]金春华,赵克森,刘杰,等.虎杖甙对休克大鼠微血管平滑肌细胞内钙、pH和膜电位的影响[J].中国药理学通报,1998,14(6)：539.
[126]李笑宏,林建海.虎杖对血流动力学、血气及纤溶系统的影响[J].上海医学,2001,24(10)：597.
[127]肖培根.新编中药志[M].第一卷.北京：化学工业出版社,2002,66-70.
[128]胡昌江,马烈,何学梅,等.九制大黄蒽醌衍生物对动物高血脂及血液流变学的影响[J].中成药,2001,23(1)：31-33.
[129]姚文兵,陈琼华.大黄的生化学研究波叶大黄多糖的抗血栓和强心作用[J].生化药物杂志,1991(1)：42-46.
[130]Sato M,Maulik G,Bagchi D.Myocardial protection by protykin,a novel extract of trans resveratrol and emodin[J].Free Radic Res,2000,32(2):135-144.
[131]周明学,徐浩,陈可骥,等.几种活血解毒中药有效部位对ApoE基因敲除小鼠主动脉粥样斑块稳定性的影响[J].中国病理生理杂志,2008,24(11)：2097-2102.
[1]廖明芳,景在平,丁茹.动脉粥样硬化血栓形成疾病的发病机制进展[J].国际病理科学与临床杂志,2006,26(2)：106-109.
[2]Cardiovascular disease:prevention and control.WHO web site.Available at:http://www. who.int/dietphysicalactivity/publications/facts/cvd/en/
[3]池明宇.中西医结合血栓病学[M].北京：人民卫生出版社,2004：38-196.
[4]陈思锋.动脉粥样硬化性初期斑块的逆转原理[J].中国动脉硬化杂志,2007,15(7)：530-531.
[5]全国高胆固醇血症控制状况多中心研究协作组.高胆固醇血症临床控制状况多中心协作研究[J].中华心血管病杂志,2002,30(2)：109-114.
[6]Boden WE,O'Rourke RA,Teo KK,et al.COURAGE Trial Research Group:Optimal medical therapy with or without PCI for stable coronary disease[J].N Engl J Med,2007, 356(15):1503-1516.
[7]Pfisterer M,Brunner-La Rocca HP,Buser PT,et al.Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents:all observational study of drug-eluting versus bare-metal stents[J].J Am Coll Cardiol,2006,48(12):2584-2591.
[8]Wlliams DO,Abbott JD,Kip KE,et al.Outcomes of 6906 patients undergoing percutaneous coronary intervention in the era of drug-eluting stents:report of the DES cover Registry[J].Circulation,2006,114(20):2154-2162.
[9]Lagerqvist B,lames SK,Stenestrand U,et al.SCAAR Study Group.Long-term outcomes with drug-eluting stents versus bare-metal stents in Sweden.N Engl J Med, 2007,356(10):1009-1019.
[10]Spaulding C,Daemen J,Boersma E,et al.A pooled analysis of data comparing sirolimus-eluting stents with bare-metal stents[J].N Engl J Med,2007,356(10):989-997.
[11]Cox DA,Steone GW,Grines CL,et al.Comparative early and late outcomes after primary percutaneous coronary intervention in ST-segment elevation and non-ST-segment elevation acute myocardial infarction(from the CADILLAC Trial)[J].Am J Cardiol,2006,98(3):331-337.
[12]Hilosch A,Windhausen F, Tijssen JG,et al.Invasive versus Conservative Treatment in Unstable coronary Syndromes(ICTUS) investigators:Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome and elevated cardiac troponin T(the ICTUS trial):a follow-up study[J].Lancet,2007,369(9564):827-835.
[13]Keeley EC,Boura JA,Grines CL.Comparison of primary and facilitated pereutaneous coronary intervention for ST-elevation myocardial infarction:quantitative review of randomized trial[J].Lancet,2006,367(9510):579-588.
[14]Hochman JS,Lamas GA,Buller CE,et al.Coronary intervention for persistent occlusion after myocardial infarction[J].N Engl J Med,2006,355 (23):2395-2407.
[15]崔新厂.血小板在动脉粥样硬化中的作用研究进展[J].临床研究2007,4(10)：96-100.
[16]马长生,张铭.抗栓药物在冠心病二级预防中的应用[J].中国医师进修杂志(内科版),2007,30(10)：7-9.
[17]Ross R.Atherosclerosis-an inflammatory disease[J].N Engl J Med,1999,340(2): 115-126.
[18]万莹,杨敏,孙刚,等.阿托伐他汀治疗颈动脉粥样硬化斑块184例临床研究[J].南通大学学报(医学版),2007,27(5)：418-419.
[19]Scientific Committee of the PERTINENT Sub-Study,EUROPA-PERTINENT Investigators:PERTINENT-perindopril-thrombosis, inflammation,endothelial dysfunction and neurohormonal activation trial:a sub-study of the EUROPA study[J].Cardiovasc Drugs Ther,2003,17(1):83-91.
[20]Hernandez-Presa MA,Bustos C,Ortego M,et al.ACE inhibitor quinapril reduces the arterial expression of NF-kappaB-dependent proinflammatory factors but not of collagen in a rabbit model of atherosclerosis[J].Am J Pathol,1998,153(6):1825-1837.
[21]Da Cunha V,Tham DM,Martin-McNulty B,et al.Enalapril attenuates angiotensin Ⅱ induced atherosclerosis and vascular inflammation[J]. Atherosclerosis, 2005,178(1):9-17.
[22]杨玲.福辛普利对兔动脉粥样硬化形成的干预作用观察[J].河北医学,2007,13(11)：1271-1273.
[23]McGeer PL,McGeer EG,Yasojima K.Expression of COX-1 and COX-2 mRNAs in atherosclerotic plaques[J].Exp Gerontol,2002,37(7):25-929.
[24]O'Connor CM,Dunne MW,Pfeffer MA,et al.Investigators in the WIZARD Study-Azithronlycin for the secondary prevention of coronary heart disease events:the WIZARD study:a randomized controlled trial[J].JAMA,2003,290(11):1459-1466.
[25]张子新,赵卫华,宋丽新,等.阿奇霉素对动脉粥样硬化家兔炎症反应的影响[J].中国动脉硬化杂志,2006,14(7)：601-603.
[26]张晓坤,沈玲红,何奔.动脉粥样硬化药物治疗的新靶点-核受体Nur77和类视黄醇×受体[J].内科理论与实践,2007,2(5)：292-294.
[27]黎鹏程,程丑夫,刘建和,等.冠状动脉脂质斑块中医病因病机探讨[J].中国中医药信息杂志,2008,15(9)：3-4.
[28]袁肇凯,田松,黄献平,等.长沙地区冠心病中医证型的临床流行病学研究[J].中华中医药学刊,2008,26(8)：1605-1608.
[29]屈岚.冠心病辩证分型研究概况及统计分析[J].中华中医药学刊,2011,29(1)：175-178.
[30]林培政.动脉粥样硬化性疾病与中医湿热证的关系[J].中药新药与临床医药,2006,17(2)：147-149.
[31]绍成五.中医对动脉粥样硬化的认识及防治进展[J].湖南中医药导报,2003,7.9(7)：23-25.
[32]杨焕斌.冠心Ⅱ号治疗颈动脉粥样硬化的临床研究(Ⅱ)[J].中国中医药科技,2005,1.12(1)：43-44.
[33]程丑夫.冠心病中医诊疗思考[J].湖南中医药大学学报,2009,29(3)：3-5.
[34]卢笑晖,王阶.国内外冠心病临床指南研究现状调查及对中医临床指南的思考[J].北京中医药大学学报(中医临床版),2007,14(4)：27-30.
[35]王阶,何庆勇.冠心病心绞痛中医疗效评价体系的思考[J].第三届世界中医药心血管学术研讨会论文全文集,2008：287-289.