中药五灵脂对动脉粥样硬化大鼠细胞间黏附分子-1的影响
|
摘要
背景动脉粥样硬化(atherosclerosis,AS)所致冠心病严重威胁着人类健康,也给家庭和社会带来了沉重负担。研究显示,AS是一种慢性炎症过程,细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)与此过程关系密切。ICAM-1属于免疫球蛋白超家族成员,主要表达于血管内皮细胞、单核细胞、淋巴细胞等,但正常情况下仅为低水平或不表达。在AS炎症发展过程中单核细胞与内皮细胞间的黏附主要靠ICAM-1介导。细胞外的黏附分子能被酶分解并在血清中检测到,称为可溶性黏附分子。中医学“胸痹心痛”相当于现代医学的冠心病心绞痛。活血化瘀中药具有很好的抗AS作用,但其机制尚不明了。本课题旨在观察五灵脂水提取物对实验性AS大鼠ICAM-1表达的影响,探讨其抗AS作用的机制,丰富中医药治疗冠心病的理论基础。
方法将健康、清洁、雄性6 w龄Wistar大鼠60只随机分为空白对照组、模型组、五灵脂低剂量组、五灵脂高剂量组,采用高脂饮食结合腹腔注射维生素D3注射液复制动脉粥样硬化模型,经病理检测证实模型复制成功后五灵脂低、高剂量组大鼠分别给予五灵脂水提取物不同剂量(2.5g/kg体重、10g/kg体重)灌胃干预。给药6 w后采用酶联免疫吸附法测大鼠血清可溶性细胞间黏附分子-1(soluble intercellular adhesion molecule-1,sICAM-1)水平,免疫组织化学法观察主动脉ICAM-1表达,透射电镜观察主动脉内膜病变情况。
结果大鼠动脉粥样硬化模型复制成功。ELISA结果显示,空白对照组大鼠血清含微量sICAM-1(为3.10±0.42 ng/ml),明显低于其它组(P<0.01)。药物干预后五灵脂低剂量组、五灵脂高剂量组大鼠血清sICAM-1(分别为42.73±6.97、21.29±4.27 ng/ml)较干预前(分别为82.26±6.72、82.41±7.06 ng/ml)显著降低,差异有统计学意义(P<0.01),也显著低于模型组(P<0.01)。免疫组化结果显示,模型组大鼠主动脉内皮细胞ICAM-1表达强阳性,药物干预后五灵脂低剂量组、五灵脂高剂量组大鼠ICAM-1表达明显减少(P<0.01),五灵脂高剂量组轻于五灵脂低剂量组(P<0.05),但仍明显高于空白对照组(P<0.05)。透射电镜结果显示,空白对照组大鼠主动脉透射电镜观察可见内皮细胞间连接紧密,无细胞肿胀、脱落等,内皮下间隙正常;模型组见内皮细胞明显肿胀,部分脱落,细胞间连接中断,表面有单核细胞黏附,内皮下泡沫细胞堆积,内皮下间隙变窄;五灵脂低剂量、五灵脂高剂量组大鼠主动脉病变明显轻于模型组,五灵脂高剂量组病变轻于五灵脂低剂量组。
结论1.高脂饲料(配方为3%胆固醇,0.5%胆酸钠,0.2%丙基硫氧嘧啶,5%白糖,10%猪油,81.3%基础饲料)配合腹腔注射维生素D3注射液能够形成大鼠AS动物模型,但该配方仍有待改进。
2.AS大鼠主动脉内皮细胞ICAM-1表达强阳性,血清sICAM-1水平明显升高,其与AS炎症关系密切。
3.中药五灵脂能抑制实验性动脉粥样硬化大鼠ICAM-1表达,减轻血管内膜病变程度,10g/kg体重剂量优于2.5g/kg体重剂量,这可能是其抗AS炎症的分子机制之一。
Background: That atherosclerosis (AS) result in coronary heart disease(CHD) acutely threatens human being’s health, and bring heavy burden to the family and society. Research display that AS is an especially kind chronic inflammation process, and intercellular adhesion molecule-1(ICAM-1)associates with this process closely. ICAM-1 is a member of the immunoglobulin superfamily, and express in vascular endothelial cell(VEC)、monocaryon(MN)、leukomonocyte(LY) etc. ICAM-1 commonly expresses lowly or doesn’t express even. In the development process of AS chronic inflammation, MNs adhere to ECs mostly by ICAM-1. Adhesion molecules out of cell can be resolved by especial enzymes and detected in blood serum that are called dissolubility adhesion molecule. In Chinese traditional medicine“XIONGBI”corresponds to CHD of Western medicine. The traditional Chinese medicine is good for the patients of CHD, but the mechanisms isn’t clear .This study is to explore the effect of Faeces Trogopteri (FT) aqueous extract on the expression of intercellular adhesion molecule (ICAM-1) and endarteropathy and its anti artherosclerosis (AS) in the experimental AS rats, and enhance the rationale of TCM for CHD.
Methods: Sixty healthy male clean six weeks Wistar rats were randomly divided into 4 groups of 15 rats per group: blank, model, FT low dose(FTL, 2.5 g/kg weight) and FT high dose (FTH, 10 g/kg weight) groups. The blank group was fed standard feedstuff, the other three groups were duplicated by feeding high cholesterol diet and peritoneal injecting vitamin D3 6 weeks later, the serum soluble intercellular adhesion molecule-1 (sICAM-1) level in the rats was measured by enzyme liked immunosorbent assay kit; the expression of ICAM-1 proteinum in the endarterium of AS rats was detected by immunohistochemical technique; the pathological changes in the endarterium of AS rats was observed by transmission electron microscope.
Results: The rat AS model was successfully duplicated. Compared with the other groups, the serum sICAM-1 level of blank group was markedly lower〔( 3.10±0.42 ) vs (81.62±7.30),(82.26±6.72) ,(82.41±7.06) ng/ml,P<0.01〕; after the FT interfering, the serum sICAM-1 level of FTL and FTH group rats was markedly lower〔(42.73±6.97) vs (82.26±6.72), (21.29±4.27) vs (82.41±7.06) ng/ml,P<0.01〕, and lower than that of model group〔(42.73±6.97) vs (85.63±11.43), (21.29±4.27) vs (85.63±11.43) ng/ml, P<0.01〕. The expression of ICAM-1 proteinum at the endarterium of FTL and FTH group rats was obviously fewer than those of model group, and those of FTL group was fewer than those of FTH group. Transmission electron microscope result showed hat the endothelial damage of the aortas in FTL and FTH groups was less severe than that in model group.
Conclusion: 1.The AS model of rat can be made by feeding HFD and injecting vitamin D3,but the prescription of HFD may need to be improved.
2. The serum soluble intercellular adhesion molecule-1 (sICAM-1) level in the AS rats is conspicuously higher than that of the blank group, which indicates that sICAM-1 correlates with AS inflammation process closely.
3. FT can downregulate the expression of ICAM-1 in the artery of experimental AS rats, and lighten the endothelial damage of the aortas, higher doe(s10 g/kg weight) is better than lower dose(2.5 g/kg weight), which may account for the anti AS effects of FT.
方法将健康、清洁、雄性6 w龄Wistar大鼠60只随机分为空白对照组、模型组、五灵脂低剂量组、五灵脂高剂量组,采用高脂饮食结合腹腔注射维生素D3注射液复制动脉粥样硬化模型,经病理检测证实模型复制成功后五灵脂低、高剂量组大鼠分别给予五灵脂水提取物不同剂量(2.5g/kg体重、10g/kg体重)灌胃干预。给药6 w后采用酶联免疫吸附法测大鼠血清可溶性细胞间黏附分子-1(soluble intercellular adhesion molecule-1,sICAM-1)水平,免疫组织化学法观察主动脉ICAM-1表达,透射电镜观察主动脉内膜病变情况。
结果大鼠动脉粥样硬化模型复制成功。ELISA结果显示,空白对照组大鼠血清含微量sICAM-1(为3.10±0.42 ng/ml),明显低于其它组(P<0.01)。药物干预后五灵脂低剂量组、五灵脂高剂量组大鼠血清sICAM-1(分别为42.73±6.97、21.29±4.27 ng/ml)较干预前(分别为82.26±6.72、82.41±7.06 ng/ml)显著降低,差异有统计学意义(P<0.01),也显著低于模型组(P<0.01)。免疫组化结果显示,模型组大鼠主动脉内皮细胞ICAM-1表达强阳性,药物干预后五灵脂低剂量组、五灵脂高剂量组大鼠ICAM-1表达明显减少(P<0.01),五灵脂高剂量组轻于五灵脂低剂量组(P<0.05),但仍明显高于空白对照组(P<0.05)。透射电镜结果显示,空白对照组大鼠主动脉透射电镜观察可见内皮细胞间连接紧密,无细胞肿胀、脱落等,内皮下间隙正常;模型组见内皮细胞明显肿胀,部分脱落,细胞间连接中断,表面有单核细胞黏附,内皮下泡沫细胞堆积,内皮下间隙变窄;五灵脂低剂量、五灵脂高剂量组大鼠主动脉病变明显轻于模型组,五灵脂高剂量组病变轻于五灵脂低剂量组。
结论1.高脂饲料(配方为3%胆固醇,0.5%胆酸钠,0.2%丙基硫氧嘧啶,5%白糖,10%猪油,81.3%基础饲料)配合腹腔注射维生素D3注射液能够形成大鼠AS动物模型,但该配方仍有待改进。
2.AS大鼠主动脉内皮细胞ICAM-1表达强阳性,血清sICAM-1水平明显升高,其与AS炎症关系密切。
3.中药五灵脂能抑制实验性动脉粥样硬化大鼠ICAM-1表达,减轻血管内膜病变程度,10g/kg体重剂量优于2.5g/kg体重剂量,这可能是其抗AS炎症的分子机制之一。
Background: That atherosclerosis (AS) result in coronary heart disease(CHD) acutely threatens human being’s health, and bring heavy burden to the family and society. Research display that AS is an especially kind chronic inflammation process, and intercellular adhesion molecule-1(ICAM-1)associates with this process closely. ICAM-1 is a member of the immunoglobulin superfamily, and express in vascular endothelial cell(VEC)、monocaryon(MN)、leukomonocyte(LY) etc. ICAM-1 commonly expresses lowly or doesn’t express even. In the development process of AS chronic inflammation, MNs adhere to ECs mostly by ICAM-1. Adhesion molecules out of cell can be resolved by especial enzymes and detected in blood serum that are called dissolubility adhesion molecule. In Chinese traditional medicine“XIONGBI”corresponds to CHD of Western medicine. The traditional Chinese medicine is good for the patients of CHD, but the mechanisms isn’t clear .This study is to explore the effect of Faeces Trogopteri (FT) aqueous extract on the expression of intercellular adhesion molecule (ICAM-1) and endarteropathy and its anti artherosclerosis (AS) in the experimental AS rats, and enhance the rationale of TCM for CHD.
Methods: Sixty healthy male clean six weeks Wistar rats were randomly divided into 4 groups of 15 rats per group: blank, model, FT low dose(FTL, 2.5 g/kg weight) and FT high dose (FTH, 10 g/kg weight) groups. The blank group was fed standard feedstuff, the other three groups were duplicated by feeding high cholesterol diet and peritoneal injecting vitamin D3 6 weeks later, the serum soluble intercellular adhesion molecule-1 (sICAM-1) level in the rats was measured by enzyme liked immunosorbent assay kit; the expression of ICAM-1 proteinum in the endarterium of AS rats was detected by immunohistochemical technique; the pathological changes in the endarterium of AS rats was observed by transmission electron microscope.
Results: The rat AS model was successfully duplicated. Compared with the other groups, the serum sICAM-1 level of blank group was markedly lower〔( 3.10±0.42 ) vs (81.62±7.30),(82.26±6.72) ,(82.41±7.06) ng/ml,P<0.01〕; after the FT interfering, the serum sICAM-1 level of FTL and FTH group rats was markedly lower〔(42.73±6.97) vs (82.26±6.72), (21.29±4.27) vs (82.41±7.06) ng/ml,P<0.01〕, and lower than that of model group〔(42.73±6.97) vs (85.63±11.43), (21.29±4.27) vs (85.63±11.43) ng/ml, P<0.01〕. The expression of ICAM-1 proteinum at the endarterium of FTL and FTH group rats was obviously fewer than those of model group, and those of FTL group was fewer than those of FTH group. Transmission electron microscope result showed hat the endothelial damage of the aortas in FTL and FTH groups was less severe than that in model group.
Conclusion: 1.The AS model of rat can be made by feeding HFD and injecting vitamin D3,but the prescription of HFD may need to be improved.
2. The serum soluble intercellular adhesion molecule-1 (sICAM-1) level in the AS rats is conspicuously higher than that of the blank group, which indicates that sICAM-1 correlates with AS inflammation process closely.
3. FT can downregulate the expression of ICAM-1 in the artery of experimental AS rats, and lighten the endothelial damage of the aortas, higher doe(s10 g/kg weight) is better than lower dose(2.5 g/kg weight), which may account for the anti AS effects of FT.
引文
[1] Hachinski V.Stroke:The next 30 years[J].Stroke,2002;33(1):1-4.
[2] Gaut JP,Heinecke JW.Mechanisms for oxidizing low-density lipoprotein.Insights from patterns of oxidation products in the artery wall and from mouse models of atherosclerosis[J].Trends Cardiovasc Med,2001;11:103-112.
[3] Schmidt-Trucksass A,Baumstark MW,Daub C,Espenschied S,Grathwohl D,Berg A. Lipoprotein phenotype and adhesion molecules correlate with diurnal triglyceride profiles in patients with coronary artery disease[J].Nutr Metab Cardiovasc Dis,2004; 14(1):20-25.
[4] Blann AD,Seigneur M,Steiner M,Miller J P,McCollum C N.Circulating ICAM-1 and VCAM-1 in peripheral artery disease and hypercholesterolaemia:relationship to the location of atherosclerotic disease,smoking,and in the prediction of adverse events[J]. Thromb Haemost,1998;79(6):1080-1085.
[5] Tang W,Pankow JS,Carr JJ,et al.Association of sICAM-1 and MCP-1 with coronary artery calcification in families enriched for coronary heart disease or hypertension: the NHLBI Family Heart Study[J].BMC Cardiovasc Disord,2007;7:30.
[6]杨鹏远,芮耀诚,焦亚斌.动脉粥样硬化大鼠实验模型的建立[J].第二军医大学学报,2003;24(7):802-804.
[7] Ohmori K,Yamada H,Yasuda A,et al.Anti-hyperlipidemic action of a newly synthesized benzoic acid derivative,S-2E[J].Eur J Pharmacol,2003;471(1):69-76.
[8] Asztalos BF,Schaefer EJ.HDL in atherosclerosis:actor or bystander[J].Atheroscler Suppl, 2003;4(1):21-29.
[9]张震,惠汝太.高密度脂蛋白和甘油三酷作为治疗的靶点[J].中国分子心脏病学杂志,2003;3(5):296-304.
[10] Nissen SE,Tuzcu EM,Schoenhagen P,et al.Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis:a randomized controlled trial[J].JAMA,2004;291(9):1071-1080.
[11] Cannon C P,Braunwald E,McCabe C H,et al.Intensive versus moderate lipid lowering with statins after acute coronary syndromes[J].N Engl J Med,2004;350(15):1495-1504.
[12] Libby P,Aikawa M,Schonbeck U.Cholesterol and atherosclerosis[J].Biochim Biophys Acta,2000;1529:299-309.
[13] LIBBY P.Inflammation in atherosclerosis[J].Nature,2002; 420(6917):868-874.
[14]王保华,欧阳静萍,刘永明,等.当归对高脂血清所致ECV304细胞损伤的保护作用[J].生理学报,2001;53(3):240-243.
[15] Mamputu JC,Renier G.Advanced glycation end-products increase monocyte adhesion to retinal endothelial cells through vascular endothelial growth factor-induced ICAM-1 expression:inhibitory effect of antioxidants[J].J Leukoc Biol,2004;75(6):1062-1069.
[16] Altannavch TS,Roubalova K,Kucera P,et al.Effect of high glucose concentrations on expression of ELAM-1, VCAM-1 and ICAM-1 in HUVEC with and without cytokine activation[J].PhysiolRes,2004;53(1):77-82.
[17] Pradhan AD,Rifai N,Rifai N,Ridker PM.Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1,and the development of symptomatic peripheral arterial disease in men[J].Circulation,2002;106(7):820-825.
[18] Haim M,Tanne D,Boyko V, et al.Soluble intercellular adhesion molecule-1 and long term risk of acute coronary events in patients with chronic coronary heart disease.Data from the Bezafibrate Infarction Prevention (BIP) Study[J].J Am Coll Cardiol,2002;39(7): 1133-1138.
[19] Wang L,Zhou GB,Liu P,et al.Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia[J].PNAS, 2008;105(12):4826-4831.
[20]马晓娟,殷惠军,陈可冀.血瘀证与炎症相关性的研究进展[J].中国中西医结合杂志,2007;27(7):669-672.
[21]胡冬裴.胸痹证治文献研究[J].山东中医药大学学报,2005;29(1):37-40.
[22]丁邦晗,严夏,林晓忠,等.血脂异常与胸痹心痛基本证型的相关性分析--365例病例资料Logistic回归分析结果[J].辽宁中医杂志,2006;33(10):1261-1262.
[23]陈可冀,李连达,翁维良,等.血瘀证与活血化瘀研究[J].中西医结合心脑血管病杂志,2005;3(1):1-2.
[24]杨雨民,周佳.程志清从瘀防治冠状动脉术后再狭窄经验[J].中医杂志,2006;47(3): 180-181.
[25]刘雅,肖茜,王超,王宗仁.芪丹通脉片治疗动脉粥样硬化的效果[J].心脏杂志,2008;20(3):2.
[26]薛梅,陈可冀,马晓娟,等.血府逐瘀口服液对冠心病血瘀证患者血液流变学的影响及其与人类血小板抗原3基因多态性的相关性[J].中西医结合学报,2008;6(11):1129-11 35.
[27]王忠建.心痛失笑散治疗冠心病心绞痛疗效观察[J].中医药临床杂志,2006;18(3): 265-266.
[28]祝光礼,陈铁龙,陈启兰,等.黄芪失笑汤为主治疗气虚血瘀型冠心病[J].浙江中西医结合杂志,2006;16(10):625-626.
[29]俞之杰.21种中草药对体外纤维蛋白溶解作用的观察[J].中西医结合杂志,1986;6(8): 484-485.
[30]王世久,刘玉兰,宋丽艳,等.五灵脂抗血小板聚集作用的药理研究[J].沈阳药学院学报, 1994;11(4):246-249.
[31]卜淑敏,贾卯花,曲运波.五灵脂对小鼠和大鼠脑缺血的保护作用[J].山西大学学报(自然科学版),2000;23(3):257-259.
[1]杨东明,苏世文,李铣,等.五灵脂活性成分的研究[J].药学学报,1987;22(10):756-760.
[2] Atsushi Numata,Peiming Yang,Chika Takahashi,et al.Cytoxic Triterpenes from a Chine -se Medicine[J]. Chem Pharm Bull, 1989;37(3):648.
[3] Atsushi Numata,Chika Takahashi,Tamie Miyayoto, et al.New Triterpenes from a Chine–se Medicine[J]. Chem Pharm Bull, 1990;38(4):942.
[4]仲崇林,李焕荣,邓明鲁,等.五灵脂化学成分的研究[J].中草药,1990;21(1):11.
[5]陈月开,周纪侃,黄淑萍,等.五灵脂无机成分的分析研究[J].中国生化药物分析,1994; 15(4):241-244.
[6]刘文粢,刘倩平,李庆明,等.五灵脂及其炮制品的微量元素含量测定[J].广东微量元素科学,2002;9(11):59-60.
[7]魏垠,张秀,黄爱今.毛细管气相色谱和气象色谱/质谱法分析五灵脂挥发性成分[J].分析化学,2001;29(2):195-198.
[8]李强,陆蕴如,鲁雪照,等.五灵脂化学成分的研究Ⅰ[ J].中国药学杂志,1999;34(80):514- 516.
[9]樊良卿.20种活血化瘀药对正常小鼠免疫调节作用的影响[J].浙江中医杂志,1992;27 (3):123-125.
[10]樊良卿,扬锋,胡利平,等.丹皮等活血化瘀药对细胞免疫功能低下小鼠的免疫调节作用[J].浙江中医杂志,1992;27(4):180-182.
[11]王世久,宋丽艳,刘玉兰,等.五灵脂乙酸乙酯提取物抗炎作用研究[J].沈阳药学院学报,1994;11(1):49-52.
[12]李庆明.五灵脂对胃粘膜保护作用的临床与实验研究[J].中国中西医结合杂志, 1996;16(2):90-92.
[13]王雄文,刘文姿,黎成科,等.五灵脂B1对大鼠胃壁结合黏液量及胃黏膜PGE2的影响[J].广东药学院学报,2004;20(5):515-516.
[14]俞之杰.21种中草药对体外纤维蛋白溶解作用的观察[J].中西医结合杂志,1986;6(8): 484-485.
[15]王世久,刘玉兰,宋丽艳,等.五灵脂抗血小板聚集作用的药理研究[J].沈阳药学院学报, 1994;11(4):246-249.
[16]陈月开,王海雄,袁勤生.五灵脂对小鼠血液中SOD活性的影响[J].中国生化药物杂志, 1994;15(3):161-164.
[17]卜淑敏,贾卯花,曲运波.五灵脂对小鼠和大鼠脑缺血的保护作用[J].山西大学学报(自然科学版),2000;23(3):257-259.
[18]陈月开,陈少松,王美素.五灵脂中黄酮类成分研究[J].山西大学学报(自然科学版), 2005;28(1):98-100.
[19]王忠建.心痛失笑散治疗冠心病心绞痛疗效观察[J].中医药临床杂志,2006;18(3):265- 266.
[20]祝光礼,陈铁龙,陈启兰,等.黄芪失笑汤为主治疗气虚血瘀型冠心病[J].浙江中西医结合杂志,2006;16(10):625-626.
[21]承小敏.加味失笑散治疗室女痛经46例[J].四川中医,2005;23(10):87-88.
[22]周英,叶敦敏.寿胎丸合失笑散治疗肾虚血瘀型先兆流产的临床疗效观察[J].广州中医药大学学报,2006;23(1):25-28.
[23]李庆明,孙维峰.五灵脂素治疗十二指肠溃疡34例临床研究[J].实用医学杂志,1994;10 (1):49-50.
[24]王培香,韩明亮.辨证治疗消化性溃疡88例[J].河南中医,2004;24(11):41-42.
[25]陈明.中西医结合治疗慢性萎缩性胃炎136例临床观察[J].甘肃中医医,2005;18(4):25- 26.
[26]贾朝阳.理气和胃止痛汤治疗慢性浅表性胃炎68例[J].实用中医药杂志,2006;22(10): 635.
[27]武水斗,伊书红.五灵脂丸治疗瘢痕疙瘩54例疗效观察[J].北京中医药大学学报(中医临床版),2006;13(4):23-24.
[28]陈颖异.外治内服辨证分型以消痛散加味治疗慢性盆腔疼痛症379例[J].中医外治杂志,2000;9(4):24-25.
[29]陈茂星,关志华,陈丽晶.自拟七味止痛饮治疗痛证[J].牡丹江医学院学报,2002;23(1): 23.
[1] Wang L, Zhou GB, Liu P, et al. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia[J].PNAS, 2008;105(12):4826-4831.
[2] [0]马晓娟,殷惠军,陈可冀.血瘀证与炎症相关性的研究进展[J].中国中西医结合杂志,2007;27(7):669-672.
[3] [0]胡冬裴.胸痹证治文献研究[J].山东中医药大学学报,2005;29(1):37-40.
[4]丁邦晗,严夏,林晓忠,等.血脂异常与胸痹心痛基本证型的相关性分析--365例病例资料Logistic回归分析结果[J].辽宁中医杂志,2006;33(10):1261-1262.
[5] [0]陈可冀,李连达,翁维良,等.血瘀证与活血化瘀研究[J].中西医结合心脑血管病杂志,2005;3(1):1-2.
[6] [0]杨雨民,周佳.程志清从瘀防治冠状动脉术后再狭窄经验[J].中医杂志,2006;47(3): 180-181.
[7] [0]丘瑞香,罗致强,朱雅宜,等.冠心病血瘀证血液理化特性与中医证型相关性研究[J].中医杂志,2002;43(5):378-379.
[8]毛以林,袁肇凯,黄献平,等.冠心病血瘀证与血管紧张素转换酶基因多态性的相关性研究[J].中国中西医结合杂志,2004;24(9):776-780.
[9]毛以林,谭光波,袁肇凯,等.高敏C-反应蛋白和可溶性细胞间黏附分子-1与冠心病血瘀证的相关性研究[J].新中医,2007;39(3):25-26.
[10]徐浩,鹿小燕,陈可冀,等.血瘀证及其兼证与冠脉造影所示病变及介入治疗后再狭窄的相关性研究[J].中国中西医结合杂志,2007;21(1):8-13.
[11]李萍,李洪,贺冬林,赵燕,等.川芎嗪注射液对小鼠缺血再灌注心肌的保护作用[J].中国医院药学杂志,2006;26(1):32-34.
[12]汤碧娥,徐庆,宋丽华,等.川芎嗪预处理对缺血再灌注离体大鼠心脏的保护作用[J].中国中医急症,2005;14(10):993.
[13]文川,徐浩,黄启福,等. Apoe缺陷小鼠动脉粥样硬化斑块的影响[J].中国病理生理杂志,2005;21(5):864-867.
[14]潘洪平,杨嘉珍,李吕力,等.葛根素注射液对急性血淤模型大鼠血液流变学及血小板聚集的影响[J].中国医院药学杂志,2005;25(1):6-8.
[15]郑惠珍,陈小源,梁洪英,等.川芎嗪对压力超负荷大鼠血液流变学的影响[J].中国血液流变学杂志,2006;16(1):9-11.
[16] [0]许冬青,张旭,蔡文峰,等.丹参药物血清保护血管内皮细胞分子机制研究[J].中成药,2005;27(2):229-230.
[17]陈剑鸿,王碧江,刘松青,等.三七总皂苷对内毒素损伤血管内皮细胞炎症特性的影响[J].中国医院药学杂志,2004;24(3):140-141.
[18] [0]陈丰,詹萍,黄碧仙.灯盏细辛注射液治疗冠心病不稳定型心绞痛[J].广东医学,2005;26(10):1424-1425.
[19]王忠建.心痛失笑散治疗冠心病心绞痛疗效观察[J].中医药临床杂志,2006;18(3):265- 266.
[20]蔡广,叶常青.三七总苷注射液治疗冠心病的疗效[J].心脏杂志,2006;18(5):562-567.
[21] [0]丁斗,董小君,加味丹参饮治疗冠心病心绞痛41例[J].长春中医药大学学报,2007;23 (3):38.
[22]王有万.复方丹参滴丸对冠心病冠状动脉侧支循环和血运重建的临床观察[J].陕西中医学院学报,2008;31(1):25-26.
[23] [0]刘雅,肖茜,王超,王宗仁.芪丹通脉片治疗动脉粥样硬化的效果[J].心脏杂志,2008;20 (3):2.
[24]薛梅,陈可冀,马晓娟,等.血府逐瘀口服液对冠心病血瘀证患者血液流变学的影响及其与人类血小板抗原3基因多态性的相关性[J].中西医结合学报,2008;6(11):1129- 1135.
[25]徐志伟,刘小斌,邱仕君,等.中医“五脏相关”理论继承与创新的初步研究[J].广州中医药大学学报,2008;25 (6):475-479.
[2] Gaut JP,Heinecke JW.Mechanisms for oxidizing low-density lipoprotein.Insights from patterns of oxidation products in the artery wall and from mouse models of atherosclerosis[J].Trends Cardiovasc Med,2001;11:103-112.
[3] Schmidt-Trucksass A,Baumstark MW,Daub C,Espenschied S,Grathwohl D,Berg A. Lipoprotein phenotype and adhesion molecules correlate with diurnal triglyceride profiles in patients with coronary artery disease[J].Nutr Metab Cardiovasc Dis,2004; 14(1):20-25.
[4] Blann AD,Seigneur M,Steiner M,Miller J P,McCollum C N.Circulating ICAM-1 and VCAM-1 in peripheral artery disease and hypercholesterolaemia:relationship to the location of atherosclerotic disease,smoking,and in the prediction of adverse events[J]. Thromb Haemost,1998;79(6):1080-1085.
[5] Tang W,Pankow JS,Carr JJ,et al.Association of sICAM-1 and MCP-1 with coronary artery calcification in families enriched for coronary heart disease or hypertension: the NHLBI Family Heart Study[J].BMC Cardiovasc Disord,2007;7:30.
[6]杨鹏远,芮耀诚,焦亚斌.动脉粥样硬化大鼠实验模型的建立[J].第二军医大学学报,2003;24(7):802-804.
[7] Ohmori K,Yamada H,Yasuda A,et al.Anti-hyperlipidemic action of a newly synthesized benzoic acid derivative,S-2E[J].Eur J Pharmacol,2003;471(1):69-76.
[8] Asztalos BF,Schaefer EJ.HDL in atherosclerosis:actor or bystander[J].Atheroscler Suppl, 2003;4(1):21-29.
[9]张震,惠汝太.高密度脂蛋白和甘油三酷作为治疗的靶点[J].中国分子心脏病学杂志,2003;3(5):296-304.
[10] Nissen SE,Tuzcu EM,Schoenhagen P,et al.Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis:a randomized controlled trial[J].JAMA,2004;291(9):1071-1080.
[11] Cannon C P,Braunwald E,McCabe C H,et al.Intensive versus moderate lipid lowering with statins after acute coronary syndromes[J].N Engl J Med,2004;350(15):1495-1504.
[12] Libby P,Aikawa M,Schonbeck U.Cholesterol and atherosclerosis[J].Biochim Biophys Acta,2000;1529:299-309.
[13] LIBBY P.Inflammation in atherosclerosis[J].Nature,2002; 420(6917):868-874.
[14]王保华,欧阳静萍,刘永明,等.当归对高脂血清所致ECV304细胞损伤的保护作用[J].生理学报,2001;53(3):240-243.
[15] Mamputu JC,Renier G.Advanced glycation end-products increase monocyte adhesion to retinal endothelial cells through vascular endothelial growth factor-induced ICAM-1 expression:inhibitory effect of antioxidants[J].J Leukoc Biol,2004;75(6):1062-1069.
[16] Altannavch TS,Roubalova K,Kucera P,et al.Effect of high glucose concentrations on expression of ELAM-1, VCAM-1 and ICAM-1 in HUVEC with and without cytokine activation[J].PhysiolRes,2004;53(1):77-82.
[17] Pradhan AD,Rifai N,Rifai N,Ridker PM.Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1,and the development of symptomatic peripheral arterial disease in men[J].Circulation,2002;106(7):820-825.
[18] Haim M,Tanne D,Boyko V, et al.Soluble intercellular adhesion molecule-1 and long term risk of acute coronary events in patients with chronic coronary heart disease.Data from the Bezafibrate Infarction Prevention (BIP) Study[J].J Am Coll Cardiol,2002;39(7): 1133-1138.
[19] Wang L,Zhou GB,Liu P,et al.Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia[J].PNAS, 2008;105(12):4826-4831.
[20]马晓娟,殷惠军,陈可冀.血瘀证与炎症相关性的研究进展[J].中国中西医结合杂志,2007;27(7):669-672.
[21]胡冬裴.胸痹证治文献研究[J].山东中医药大学学报,2005;29(1):37-40.
[22]丁邦晗,严夏,林晓忠,等.血脂异常与胸痹心痛基本证型的相关性分析--365例病例资料Logistic回归分析结果[J].辽宁中医杂志,2006;33(10):1261-1262.
[23]陈可冀,李连达,翁维良,等.血瘀证与活血化瘀研究[J].中西医结合心脑血管病杂志,2005;3(1):1-2.
[24]杨雨民,周佳.程志清从瘀防治冠状动脉术后再狭窄经验[J].中医杂志,2006;47(3): 180-181.
[25]刘雅,肖茜,王超,王宗仁.芪丹通脉片治疗动脉粥样硬化的效果[J].心脏杂志,2008;20(3):2.
[26]薛梅,陈可冀,马晓娟,等.血府逐瘀口服液对冠心病血瘀证患者血液流变学的影响及其与人类血小板抗原3基因多态性的相关性[J].中西医结合学报,2008;6(11):1129-11 35.
[27]王忠建.心痛失笑散治疗冠心病心绞痛疗效观察[J].中医药临床杂志,2006;18(3): 265-266.
[28]祝光礼,陈铁龙,陈启兰,等.黄芪失笑汤为主治疗气虚血瘀型冠心病[J].浙江中西医结合杂志,2006;16(10):625-626.
[29]俞之杰.21种中草药对体外纤维蛋白溶解作用的观察[J].中西医结合杂志,1986;6(8): 484-485.
[30]王世久,刘玉兰,宋丽艳,等.五灵脂抗血小板聚集作用的药理研究[J].沈阳药学院学报, 1994;11(4):246-249.
[31]卜淑敏,贾卯花,曲运波.五灵脂对小鼠和大鼠脑缺血的保护作用[J].山西大学学报(自然科学版),2000;23(3):257-259.
[1]杨东明,苏世文,李铣,等.五灵脂活性成分的研究[J].药学学报,1987;22(10):756-760.
[2] Atsushi Numata,Peiming Yang,Chika Takahashi,et al.Cytoxic Triterpenes from a Chine -se Medicine[J]. Chem Pharm Bull, 1989;37(3):648.
[3] Atsushi Numata,Chika Takahashi,Tamie Miyayoto, et al.New Triterpenes from a Chine–se Medicine[J]. Chem Pharm Bull, 1990;38(4):942.
[4]仲崇林,李焕荣,邓明鲁,等.五灵脂化学成分的研究[J].中草药,1990;21(1):11.
[5]陈月开,周纪侃,黄淑萍,等.五灵脂无机成分的分析研究[J].中国生化药物分析,1994; 15(4):241-244.
[6]刘文粢,刘倩平,李庆明,等.五灵脂及其炮制品的微量元素含量测定[J].广东微量元素科学,2002;9(11):59-60.
[7]魏垠,张秀,黄爱今.毛细管气相色谱和气象色谱/质谱法分析五灵脂挥发性成分[J].分析化学,2001;29(2):195-198.
[8]李强,陆蕴如,鲁雪照,等.五灵脂化学成分的研究Ⅰ[ J].中国药学杂志,1999;34(80):514- 516.
[9]樊良卿.20种活血化瘀药对正常小鼠免疫调节作用的影响[J].浙江中医杂志,1992;27 (3):123-125.
[10]樊良卿,扬锋,胡利平,等.丹皮等活血化瘀药对细胞免疫功能低下小鼠的免疫调节作用[J].浙江中医杂志,1992;27(4):180-182.
[11]王世久,宋丽艳,刘玉兰,等.五灵脂乙酸乙酯提取物抗炎作用研究[J].沈阳药学院学报,1994;11(1):49-52.
[12]李庆明.五灵脂对胃粘膜保护作用的临床与实验研究[J].中国中西医结合杂志, 1996;16(2):90-92.
[13]王雄文,刘文姿,黎成科,等.五灵脂B1对大鼠胃壁结合黏液量及胃黏膜PGE2的影响[J].广东药学院学报,2004;20(5):515-516.
[14]俞之杰.21种中草药对体外纤维蛋白溶解作用的观察[J].中西医结合杂志,1986;6(8): 484-485.
[15]王世久,刘玉兰,宋丽艳,等.五灵脂抗血小板聚集作用的药理研究[J].沈阳药学院学报, 1994;11(4):246-249.
[16]陈月开,王海雄,袁勤生.五灵脂对小鼠血液中SOD活性的影响[J].中国生化药物杂志, 1994;15(3):161-164.
[17]卜淑敏,贾卯花,曲运波.五灵脂对小鼠和大鼠脑缺血的保护作用[J].山西大学学报(自然科学版),2000;23(3):257-259.
[18]陈月开,陈少松,王美素.五灵脂中黄酮类成分研究[J].山西大学学报(自然科学版), 2005;28(1):98-100.
[19]王忠建.心痛失笑散治疗冠心病心绞痛疗效观察[J].中医药临床杂志,2006;18(3):265- 266.
[20]祝光礼,陈铁龙,陈启兰,等.黄芪失笑汤为主治疗气虚血瘀型冠心病[J].浙江中西医结合杂志,2006;16(10):625-626.
[21]承小敏.加味失笑散治疗室女痛经46例[J].四川中医,2005;23(10):87-88.
[22]周英,叶敦敏.寿胎丸合失笑散治疗肾虚血瘀型先兆流产的临床疗效观察[J].广州中医药大学学报,2006;23(1):25-28.
[23]李庆明,孙维峰.五灵脂素治疗十二指肠溃疡34例临床研究[J].实用医学杂志,1994;10 (1):49-50.
[24]王培香,韩明亮.辨证治疗消化性溃疡88例[J].河南中医,2004;24(11):41-42.
[25]陈明.中西医结合治疗慢性萎缩性胃炎136例临床观察[J].甘肃中医医,2005;18(4):25- 26.
[26]贾朝阳.理气和胃止痛汤治疗慢性浅表性胃炎68例[J].实用中医药杂志,2006;22(10): 635.
[27]武水斗,伊书红.五灵脂丸治疗瘢痕疙瘩54例疗效观察[J].北京中医药大学学报(中医临床版),2006;13(4):23-24.
[28]陈颖异.外治内服辨证分型以消痛散加味治疗慢性盆腔疼痛症379例[J].中医外治杂志,2000;9(4):24-25.
[29]陈茂星,关志华,陈丽晶.自拟七味止痛饮治疗痛证[J].牡丹江医学院学报,2002;23(1): 23.
[1] Wang L, Zhou GB, Liu P, et al. Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia[J].PNAS, 2008;105(12):4826-4831.
[2] [0]马晓娟,殷惠军,陈可冀.血瘀证与炎症相关性的研究进展[J].中国中西医结合杂志,2007;27(7):669-672.
[3] [0]胡冬裴.胸痹证治文献研究[J].山东中医药大学学报,2005;29(1):37-40.
[4]丁邦晗,严夏,林晓忠,等.血脂异常与胸痹心痛基本证型的相关性分析--365例病例资料Logistic回归分析结果[J].辽宁中医杂志,2006;33(10):1261-1262.
[5] [0]陈可冀,李连达,翁维良,等.血瘀证与活血化瘀研究[J].中西医结合心脑血管病杂志,2005;3(1):1-2.
[6] [0]杨雨民,周佳.程志清从瘀防治冠状动脉术后再狭窄经验[J].中医杂志,2006;47(3): 180-181.
[7] [0]丘瑞香,罗致强,朱雅宜,等.冠心病血瘀证血液理化特性与中医证型相关性研究[J].中医杂志,2002;43(5):378-379.
[8]毛以林,袁肇凯,黄献平,等.冠心病血瘀证与血管紧张素转换酶基因多态性的相关性研究[J].中国中西医结合杂志,2004;24(9):776-780.
[9]毛以林,谭光波,袁肇凯,等.高敏C-反应蛋白和可溶性细胞间黏附分子-1与冠心病血瘀证的相关性研究[J].新中医,2007;39(3):25-26.
[10]徐浩,鹿小燕,陈可冀,等.血瘀证及其兼证与冠脉造影所示病变及介入治疗后再狭窄的相关性研究[J].中国中西医结合杂志,2007;21(1):8-13.
[11]李萍,李洪,贺冬林,赵燕,等.川芎嗪注射液对小鼠缺血再灌注心肌的保护作用[J].中国医院药学杂志,2006;26(1):32-34.
[12]汤碧娥,徐庆,宋丽华,等.川芎嗪预处理对缺血再灌注离体大鼠心脏的保护作用[J].中国中医急症,2005;14(10):993.
[13]文川,徐浩,黄启福,等. Apoe缺陷小鼠动脉粥样硬化斑块的影响[J].中国病理生理杂志,2005;21(5):864-867.
[14]潘洪平,杨嘉珍,李吕力,等.葛根素注射液对急性血淤模型大鼠血液流变学及血小板聚集的影响[J].中国医院药学杂志,2005;25(1):6-8.
[15]郑惠珍,陈小源,梁洪英,等.川芎嗪对压力超负荷大鼠血液流变学的影响[J].中国血液流变学杂志,2006;16(1):9-11.
[16] [0]许冬青,张旭,蔡文峰,等.丹参药物血清保护血管内皮细胞分子机制研究[J].中成药,2005;27(2):229-230.
[17]陈剑鸿,王碧江,刘松青,等.三七总皂苷对内毒素损伤血管内皮细胞炎症特性的影响[J].中国医院药学杂志,2004;24(3):140-141.
[18] [0]陈丰,詹萍,黄碧仙.灯盏细辛注射液治疗冠心病不稳定型心绞痛[J].广东医学,2005;26(10):1424-1425.
[19]王忠建.心痛失笑散治疗冠心病心绞痛疗效观察[J].中医药临床杂志,2006;18(3):265- 266.
[20]蔡广,叶常青.三七总苷注射液治疗冠心病的疗效[J].心脏杂志,2006;18(5):562-567.
[21] [0]丁斗,董小君,加味丹参饮治疗冠心病心绞痛41例[J].长春中医药大学学报,2007;23 (3):38.
[22]王有万.复方丹参滴丸对冠心病冠状动脉侧支循环和血运重建的临床观察[J].陕西中医学院学报,2008;31(1):25-26.
[23] [0]刘雅,肖茜,王超,王宗仁.芪丹通脉片治疗动脉粥样硬化的效果[J].心脏杂志,2008;20 (3):2.
[24]薛梅,陈可冀,马晓娟,等.血府逐瘀口服液对冠心病血瘀证患者血液流变学的影响及其与人类血小板抗原3基因多态性的相关性[J].中西医结合学报,2008;6(11):1129- 1135.
[25]徐志伟,刘小斌,邱仕君,等.中医“五脏相关”理论继承与创新的初步研究[J].广州中医药大学学报,2008;25 (6):475-479.