摘要
目的:本课题在论证冠心病稳定型心绞痛(心阴不足兼心血瘀阻证)基本病机和养阴活血基本治法基础上,观察复方广枣胶囊对冠心病心绞痛(心阴不足兼心血瘀阻证)患者症状和血清IL-6水平的影响,初步评价其临床安全性和有效性并探讨其部分临床作用机制。
方法:本研究采用区组随机、双盲单模拟、阳性药平行对照的设计方法。共纳入心阴不足兼心血瘀阻证冠心病稳定型心绞痛患者92例,随机分为试验组59例,对照组33例。两组在年龄、性别、病程、病情等一般临床资料方面差异无统计学意义。试验组予复方广枣胶囊,对照组予滋心阴胶囊治疗,疗程28天。治疗前后观察心绞痛症状、中医症状、硝酸甘油停减率、心电图和和血清IL-6水平及血常规、尿常规、便常规、肝功、肾功等安全性指标的变化。
结果:试验组患者心绞痛症状疗效、心电图疗效、硝酸甘油停减率的总有效率分别为83.96%、66.98%、94.12%:优于对照组的83.02%、60.00%、93.75%,但两组间比较无统计学差异(P＞0.05)。各项中医症状疗效两组间比较无统计学差异(P＞0.05)。安全性评价方面,此次临床试验未见与临床试验用药有关的安全性异常指标或异常加重指标,提示本品有较好的安全性。炎症反应方面,疗后两组血清IL-6水平均较前降低,与疗前比较差异有显著统计学意义(P＜0.01),两组对炎症反应的改善作用经q检验,差异无统计学意义(P＞0.05)。
结论:
1.复方广枣胶囊是治疗冠心病稳定型心绞痛的一个安全、有效制剂。
2.养阴活血法是治疗稳定型心绞痛心阴不足心血瘀阻证的有效治法。
3.复方广枣胶囊能显著降低稳定型心绞痛患者血清IL-6水平,抑制血管内皮炎症反应,这可能是其治疗冠心病心绞痛的作用机制之一。
Objective:To discuss the elementary pathogenesis of stable angina pectoris with the syndrome of Yin deficiency and blood stasis and the method of supplementing Yin and promoting blood flow to treat angina pectoris,study the curative effect mechanism of Compound Guangzao capsule on clinical symptom and IL-6 level in patients and discuss part of its clinical mechanism.
Methods:According to the principle of block-radomize,double-blind, single-simulate,parallel contrast controlled design,we select a total of 92 angina pectoris patients with the syndrome of Yin insufficiency and blood stasis were observed.They were divided into two groups at random.The treatment group and the control group had 59 and 33 patients.There was no obvious difference in age,sex,illness course and severity degree between the two groups.The treatment group received Complex Guangzao capsule treatment.The control group received Zixinyin capsule.The changes of clinical symptoms and laboratory indexes in all patients were observed before and after treatment.
Results:The treatment group was better than control group in overall effective rates of angina pectoris(83.96%vs 83.02%),electrocadiogram effective rate(66.98%vs 60.00%)and the reducing use rate of Nitroglycerin (89.62%vs 84.91%).At the aspect of treatment effect of traditional medicine,both groups could ameliorate the traditional Chinese medicine symptoms of angina pectoris of type Yin insufficiency and blood stasis such as chest pain,chest distress,cardiopalmus and so on.But between the experiment and control groups there was no significant difference.But there was no statistical difference between the two groups(P＞0.05).In Inflammatory reaction,IL-6 decreased.They were better and had remarkable difference than before treatment(P＜0.01).Compared between the two groups,there was no statistical difference.In side effects,no obvious and serious side effects were found.
Conclusions:
1.Compound Guangzao capsule is a safe and effective preparation on the treatment of stable angina patients.
2.The methods of Supplement yin and promoting blood circulation are effective in treatment of stable angina patients with heart Yin insufficiency and blood stasis.
3.Compound Guangzao capsule can decrease the consistency of IL-6 and Inhibiting the Inflammatory reaction of blood vessel endothelium remarkably in the stable angina patients,which may be one of mechanism action to treat coronary heart disease myocardial ischemia.
引文
1 徐瑛.中医辨证治疗冠心病60例[J].辽宁中医杂志.2002,29(7):409-410
2 朱寅圣,朴吉花.任应秋教授辨治冠心病经验[J].中国中医药信息杂志.2003,(5):63-65
2 赵益业,林晓忠,张敏州等.邓铁涛教授以心脾相关学说诊治冠心病经验介绍[J].新中医.2007,4(39):5-6
3 阎洪臣.略谈胸痹心痛的病理与症治[J].陕西新医药.1979,(6):49
4 姚真敏.《金匮要略》胸痹心痛短气证治与冠心病[J].浙江中医学院学报.1986,(4):13
6 尹克春,罗翌,刘涛.冠心病心绞痛中医证候研究概况[J].中华内科杂志.2002,19(1):2
7 陈在喜.心血管系统疾病近十年的主要进展[J].中华内科杂志.1992,31(5):479
8 1980年全国冠心病辨证论治研究座谈会.冠心病中医辨证试行标准[S].中医杂志.1980,(8):46
9 陈贵延,薛赛琴.最新国内外疾病诊疗标准[S].北京:学苑出版社,1992,209-212
10 中国中西医结合学会心血管学会.冠心病中医辨证标准[J].中西医结合杂志.1991,11(5):257
11 陈佑邦,丁泽民,干祖望等.中医病证诊断疗效标准[M].南京:南京大学出版社,1994,18-19
12 王永炎.中医内科学[M].上海:上海科学技术出版社,1997
13 李浩,孙志梅.心血管病中西医汇通[M].沈阳:辽宁科学技术出版社,2002,145-146
14 权文方.冠心病的辨证分型施治[J].实用中医内科杂志.2002,16(3):165
15 王文革,姚红芳.冠心病心绞痛的中医辨证分析[J].中西医结合心脑血管病杂志[J].2004,2(12):730
16 唐耀平,刘鹰,方显明.56例冠心病病人辨证论治分析[J].中西医结合心脑血管病杂志.2004,2(9):508
17 旷惠桃,潘远根.冠心病心绞痛临床证型分类探讨[J].中医杂志.1997,38(12):742
18 衷敬柏,董绍英,王阶等.2689例冠心病心绞痛证候要素的文献统计分析[J].中国中医药信息杂志.2006,13(5):100-101
19 杨徐航,汶医宁,魏敏慧等.冠心病中医辨证与血清C反应蛋白的相关性研究[J].中医药学刊.2004,22(9):1649
20 Braunwaid.心脏病学[M].第5版.北京:人民卫生出版社,2002:1020
21 于顾然,贺燕勤,郭云庚等.冠心病中医证型与胰岛素抵抗、脂质及RBC膜ATP酶关系的研究[J].中医杂志.2002,41(2):111
22 严卉,胡晓晟,陈君柱等.血浆同型半胱氨酸和冠状动脉粥样硬化严重程度与中医证型的关系[J].中国中西医结合杂志.2002,22(11):813
23 孔丽君.冠心病患者血浆同型半胱氨酸水平与辨证分型相关性研究[J].实用中西医结合临床.2004,4(1):7
24 方建伟,黄源鹏,林求诚等.冠心病中医证型与血浆ET、TXA_2、PGI_2的关系[J].实用中医药杂志.2005,21(9):519
25 Executive summary of the third report of the National Choles-terol Education Program(NCEP) expert panel on detection,e-valuation,and treatment of high blood cholesterol in adults(adulttreatmentpanel Ⅲ)[J].JAMA,2001,285:2486.
26 陶寿淇,吴锡桂,周北凡.中国人群心血管病危险因素作用特点的前瞻性研究[J].中华流行病学杂志[J].2005,26(1):59
27 赵亚莉,杨幼新.冠心病心电图与中医辨证分型的关系[J].江苏中医.2001,22(9):20
28 张丽萍,张向力,唐巍.冠心病中医辨证分型与左心功能的关系临床研究[J].中国中医药信息杂志.2001,8(7):50
29 林金忠,蔺德明.冠心病本虚标实证者左心室功能和结构变化研究[J].实用中医药杂志.2001,17(12):3
30 尹克春,周文斌,陈力等.89例冠状动脉造影与冠心病中医证型相关性研究[J].中医研究.2005,18(4):25
31 李静,张继东,刘同涛.冠心病中医证型与冠脉病变的相关性研究[J].山东中医药大学学报.2006,30(2):124
32 张鹏,徐伟建.中医证型与冠状动脉病变程度的相关性研究[J].中西医结合心脑血管病杂志.2007,5(2):101
33 刘华峰,程伟,李玉红.冠心病患者中医证型与冠状动脉Gensini积分、病变支数的相关性研究[J].湖北中医学院学报.2006,8(2):10.
34 马晓昌,尹太英,陈可冀等.冠心病中医辨证分型与冠状动脉造影所见相关性比较研究[J].中国中西医结合杂志.2001,21(9):654.
35 Mollet NR,Cademartiri F,NiemanK,et al.Multislice spi-ral computed tomography coronary angiography in patients withstable angina pectoris[J].J Am Coll Cardiol, 2004,43(12):2265.
36 Jeffrey J,Christie B,Nicol Ruff,et al.Comparison of ac-curacy of 64-slice cardiovascular computed tomographywith coro-nary angiography in patients with suspected coronary artery dis-ease[J].Am J Cardiol,2006,97:173.
37 迟永辉,杨新春,王乐丰等.64排CT诊断冠状动脉病变107例分析[J].中国误诊学杂志.2007,7(4):802
38 蒋瑾,付凯.双源CT的临床应用[J].实用医院临床杂志.2006,3(5):89.
39 潘涛,陈晓虎.冠心病中医辨证客观指标探讨[J].南京中医药大学学报.2007,23(6):407-408
40 黄大兰.冠心病心绞痛证治研究进展[J].实用中医药杂志.2007,23(171):269-271
41 赵永强.冠心病心绞痛脏腑辨证的临床意义[J].中西医结合心脑血管杂志.2003,1(11):673
42 陈邦倚,攀兆红.养心舒肝汤治疗心绞痛160例[J].实用中西医结合杂志.1997,10(15):1479
43 孙继铭,刘镇某,柳青林.从肝风论治冠心病心绞痛[J].实用中西医结合杂志.1997,10(20):1994
44 沈丽.益气活血法治疗老年冠心病心绞痛60例[J].北京中医药大学学报.2000,23:101
45 林坚,杨焕.补肾法对冠心病心绞痛影响[J].中国中医药信息杂志.2002,9(9):16
46 陈萍,刘桂廷.刘桂廷从肺论治冠心病心绞痛的经验[J].陕西中医.2002,22(8):720
47 张万义.从升补宗气论治老年冠心病心绞痛[J].湖北中医杂志.2003,25(5):27
48 方军.无症状性心肌缺血从脾论治体会[J].河南中医学院学报.2004,19(3):43
49 朱有银.胸痹心痛从腑论治89例[J].湖南中医药导报.1997,3(6):61
50 吴以岭.从络病学说论治冠心病心绞痛[J].中国中医基础医学杂志.2001,7(4):71
51 韩学杰,沈绍功.冠心病心绞痛痰瘀互结证的本质探讨[J].中国中医基础医学杂志.2002,82(10):53
52 韩学杰.痰瘀同治方治疗冠心病心绞痛的临床研究[J].中国中医急症.1999,8(5):212
53 张页.补气祛痰方治疗冠心病心绞痛的临床研究[J].中国中医急症.1999,8(5):207
54 权文芳.冠心病的辨证分型施治实用[J].中医内科杂志.2002,16(3):165
55 乔运河,彭红芹.冠心病的辨证用药[J].河南中医.2003,23(3):40
56 牟大鹏.以胸闷为主症的冠心病的辨证论治[J].现代中西医结合杂志.2006,15(8):1008
57 邝开安.右归丸为主方治疗冠心病心绞痛40例[J].陕西中医.2005,26(7):632-633.
58 何银辉,蔡奕,罗仕德.加味瓜蒌薤白半夏汤治疗冠心病心绞痛58例临床观察[J].中医药导报.2006,12(2):21-23.
59 严华.黄连温胆汤加减治疗冠心病心绞痛54例总结[J].湖南中医杂志.2005,21(3):19-20.
60 张艳华.膈下逐瘀汤治疗冠心病心绞痛38例[J].时珍国医国药.2005,16(1):45-46.
61 李萍.柔肝解郁汤治疗冠状动脉粥样硬化性心脏病心绞痛35例[J].河北中医.2003,25(2):98-99.
62 王进.疏肝通瘀汤治疗SAP临床观察[J].中成药.2005,27(1):120-121.
63 董德保.祛瘀化痰汤治疗冠心病心绞痛52例[J].湖北中医杂志.2004,26(4):43.
64 吕红敏.冠心通脉散加减治疗冠心病心绞痛35例[J].中国中西医结合杂志.2003,23(1):69-70.
65 陈云玺.补气通脉汤治疗冠心病心绞痛50例[J].河南中医.2003,23(1):34-35.
66 马贤珍,张成立,贾凤华.复方丹参滴丸治疗冠心病心绞痛疗效观察[J].现代中西医结合杂志.2006,15(4):420.
67 林超岱.中药通心络胶囊治疗冠心病心绞痛的研究[J].中国中医药科技.1998,5(3):172.。
68 罗陆一.麝香保心丸治疗冠心病心绞痛临床疗效观察[J].中成药.2003,25(12):984-986.
69 高建苑,孙静,苏惠等.心通口服液治疗UA疗效观察[J].中国中医急症.2003,12(2):99-100.
70 周一薇.灯盏细辛注射液治疗冠心病心绞痛50例[J].福建中医药.2002,33(3):7.
71 仲伟琴.中药注射剂治疗冠心病心绞痛研究进展.湖北中医学院学报.2006,8(3):63-65
72 乌汗毕力格等.冠心病的蒙医学范畴及其病因病机探讨[J].中国民族医药杂志.2005,6(4):27
73 琪格其图,斯琴其木格,乌尼塞音等.中国蒙古学文库·现代蒙医学[M].沈阳:辽宁民 族出版社,2002,5:227
74 布仁达来,乌仁图稚.蒙医对冠心病诊治的探讨[J].中国民族医药杂志.1996,2(2):7-8
75 白满良,杨阿敏.冠心病的蒙医学病因病机、分型及蒙医药治疗进展[J].基层医学论坛.2007,11(7):652-653
76 苏荣扎布.苏荣扎布教授治疗心脏病的经验[M].上海中医药杂志.2006,40(10):8
77 策·苏荣扎布,罗布桑,巴·吉格米德等.蒙医内科学[M].北京:民族出版社,1989,266
78 白清云,苏荣扎布,嘎拉僧等.中国医学百科全书·蒙医学分卷[M].上海:上海科学技术出版社,1992,12:73
79 叶任高,陆再英等.内科学第6版[M].北京:人民卫生出版社,2004,2(6):283
80 伊兰,纳顺达来.蒙医心刺痛与变异性心绞痛ST段电交替—附1例报告[J].中国民族医药杂志.2007,12(12):22-23
81 乌汗毕力格,莫日根图,苏和等.冠心病的蒙医学范畴及其病因病机探讨[J].中国民族医药杂志.2005,12(6):27-28
82 奥·乌力吉,孙志坚,张特日根等.倬力冠心康胶囊治疗冠心病心绞痛疗效观察[J].中国民族医药杂志.1998,4(3):12-13
83 陈巴特尔,陈其其格,阿拉塔.蒙药治疗心刺痛病临床体会[J].中国民族医药杂志.1999,5(增刊):26
84 齐华等.蒙药赞丹-3口服液治疗冠心病心绞痛临床观察[J].中国民族医药杂志.2000,6(4):11-12
85 齐太宝等.蒙药治疗冠心病心绞痛50例[J].中国民族医药杂志.2000,6(4):20
86 吴启忠,刘法,白桦等.蒙药广枣蝎蜈丸治疗冠心病心绞痛30例临床观察[J].中国民族医药杂志.2001,7(4):11
87 阿拉坦,乌力吉.蒙医药治疗冠心病100例观察[J].中国民族医药杂志.1998,4(4):23
88 奥·乌力吉等.心血舒通胶囊治疗冠心病心绞痛疗效观察[J].中国民族医药杂志.2003,9(1):5-6
89 贺力嘎等.三味广枣胶囊治疗冠心病心绞痛临床观察[J].中国民族医药杂志.2002,8(4):17-18
90 包长山等.蒙成药新-Ⅱ号治疗冠心病的临床观察[J].辽宁中医杂志.2006,33(9):1140
91 海龙,双福,胡春花.蒙医治疗冠心病的研究进展[J].中国民族医药杂志.2006,2(1):42-43
92 叶任高,路再英等.第6版.内科学[M].北京:人民卫生出版社
93 陈明哲主编.心脏病学[M].北京:北京医科大学出版社,1999:1053-1069
94 LusisAJ.Atherosclerosis[J].Nature,2000,(407):233-241
95 RaJavashisth TB,Andalibi A.Tertito MC,et al,Induction of endothelial cell expression of granulovyte and macrophage colonystimulating factors by modified low-density lipoproteins.Narure.1990,344(6263):254-257
96 Treasure CB,Klein JL,weintraub WS,et al.Beneficial effects of cholesterol lowering thetapy on the coronary endothelium in patients with chornary artery disease.N Engl Jmed,1995,332(8):481-487
97 Ross R.Cell biology of atherosclerosis[J].Ann Rev Physiol,1995,57:791-795
98 陈纪林.防治动脉粥样硬化的新动向[J].中国循环杂志.2001,16:163-166
99 牛楠.炎症与急性冠脉综合征[J].心血管病学进展.2003,24(2):137-138
100 Jan H.Von Der Thusen,Johan Kuiper,Theo JC.Van Berkel,et al Intermeukins in atherosclerosis:molecular pathways and therapeutic potential.Pharmacol Rev,2003,55:133-166
101 Balbay Y,Tikiz H,Baptiste RJ,et al.Circulating interlekin-1β,inter leukin-6,tumor necrosis factor-α,and soluble ICAM-1 in patients with chronic stable angina and myocardialinfarcton.Angiology,2001,52:109-114
102 Atalar E,Aytemir K,Haznedaroglu I,et al.Increased plasma levels of soluble selectins in Patients with unstable angina.Int J Cardiol,2001,78:69-73
103.Soeki T,Tamura Y,Shinohara H,et al.Increased soluble platelet/endothelial cell adhesion molecule-1 in the early stages of acute coronary syndromes.Int J Cardiol,2003,90(2-3):261-268
104 Verma S,Yeh1ETH.C-reactive protein and atherombosis-beyond abiomarker:an actual partaker of lesion formation.Am J physiol Regul Integr comp physiol,2003,285(5):R1253-1256
105 赵莲.炎症、动脉粥样硬化和心脑血管疾病[J].心血管病学进展.2005,26(2):194.
106 万全福.摘译冠心病的新发病因素[J].心血管病学进展.2005,21(6):382
107Eikelboom JW,Hankey GJ,von Hundelshausen PB,et al.Associations of homo -cysteine,C-reactiveprotein and cardiovascualr disease in patients with renal disease.Curr Opin Nephrol Hypertens,2001,10(3):377-383.
108 张丽君.肺炎衣原体与动脉粥样硬化关系的病理学探讨[J].中国心血管杂志.2005,10(2):84-86
109 EzzahiriR,Stassen FRM,Kurvers HAJM,et al.Chlamydia pnenmoniae infection iinduces an unstable atherosclerotic plaque phenotype inLDL-receptor,ApoE double knockout mice.Eur J Vasc Endovasc Surg,2003,26:89-95
110 夏效东.动脉粥样硬样斑块的研究现状[J].中国心血管杂志.2005,10(2):140
111 Schonbeck U,Sukhova CK.Inhibition of CD40 signaling limits evolution of established atherosclerosis in mice.Proc Natl Acad Sci USA.2000,97(13):458-463
112 Palinski W,Ord V A,Plump A S,et al.ApoE-deficientmice are a model of lipop rotein oxidation in atherogenesis.Demonstration of oxidation specific ep itopes in lesions and high titers of autoantibodies to malondialdehydelysine in serum [J].A rterioscler Thromb,1994,14(4):605-16
113 Tornvall P,Waeg G,Nilsson J,et al.Autoantibodies againstmodified low density lipoproteins in coronary artery disease[J].A therosclerosis,2003,167
114 Persson GR,Pettersson T,Ohlsson O,et al.High- sensitivityserum C- reactive protein levels in subjects with or without my-ocardial infarction or periodontitis.J Clin Periodontol,2005,32:219-224
115 郑莜萸.中药新药临床研究指导原则(试行)[S].北京:中国医药科技出版社,2002:68-72
116 Taniguchi H,Momiyama Y,Ohmori R,et al.Associations ofplasma C-reactive protein levelswiththe presence and extent ofcoronary stenosis in patients with stable coronary artery disease.Athero- sclerosis,2005,178:173-177
117 马晓静,邵建华,张兴华.切割球囊血管成型术对C-反应蛋白白细胞介素-6及细胞间粘附分子的影响[J].心肺血管病杂志.2003,22:204-207
118 王易,杨跃进.细胞因子在冠心病中的作用研究进展[J].中华心血管病杂志.2003,31(12):950-952
119 容兆宇.血府逐瘀汤对37例冠心病心绞痛患者细胞因子及氧自由基的影响[J]. 中医研究.2006,19:26-28
120 洪永敦,黄衍寿,陈宇鹏.清热化痰活血法治疗冠心病不稳定型心绞痛临床研究[J].辽宁中医杂志.2005,32:625-627
121 范利锋,陈汉玉,王平仁.稳心颗粒对不稳定型心绞痛病人hs-CRP、IL-6、TNF-α及SICAM-1的影响[J].中西医结合心脑血管病杂志.2006,4:943-945
122 邵敏,徐岩.丹参注射液治疗不稳定型心绞痛的临床研究[J].安徽中医学院学报.2003,22:13-16
123 罗镝,潘德茂.中药复方制剂通心络对心绞痛患者血.湍细胞因子影响的研究[J].新医学.2006,37:171-173
124 庄庭怡,毛静远.冠心病心绞痛与肿瘤坏死因子-α、白介素-1β及白介素-6关系的研究概况[J].中国心血管病研究.2007,5(8):613-615
125 Ursella S,Mazzone M,Portale G,et al.How to use the C-reactive.protein in cardiac disease.Minerva cardioangiol,2005,53:59-68