解毒活血法干预急性冠脉综合征的临床与实验研究
|
摘要
背景
毒壅血瘀为急性冠脉综合征的基本病机所在,根据导师多年临床经验及复习近年来多项临床研究显示,解毒活血法可不同程度地减轻机体的炎症反应,调节脂质代谢,提高机体抗缺氧能力和抗细胞凋亡的作用,减轻心肌细胞凋亡,提高患者生存质量。
目的
评价解毒活血法治疗急性冠脉综合征1个月后临床疗效和安全性,旨在初步观察解毒活血法干预急性冠脉综合征患者的临床疗效及作用机制,并对中医药的疗效作出客观评价；实验方面,采用大鼠垂体后叶素造模心肌缺血动物模型,以解毒活血法进行干预,并设立对照组,进一步明确解毒活血法在急性冠脉综合征中的治疗作用,从而为临床的治疗效果提供更有力的实验证据。
方法
对符合本研究纳入条件的80例急性冠脉综合征患者随机分为治疗组和对照组,对照组予以西医规范化治疗,治疗组在西医规范化处理基础上加用解毒活血汤进行干预。在严格按照临床研究设计的基础上,对纳入两组患者进行组间比较及治疗前后比较,通过分析治疗前后疗效指标、中医证候疗效指标、主要疗效指标、实验室炎症指标及肝肾功能等情况的变化,进行治疗前后的比较,安全性指标及不良反应、实验室检查和心电图等。进而分析治疗前后实验室指标及血清IL-1、TNF-a、SCD40L及MMP-9等相关资料的变化关系,通过统计学分析、探讨解毒活血法对急性冠脉综合征患者作用的机制所在。动物实验方法：以大鼠垂体后叶素造模心肌缺血为动物模型,以心酶、心电图及炎症介质标志物IL-1、TNF-a作为观察指标,观察解毒活血汤高、中、低剂量组(32g、16g、8g/kg)的治疗效果,采用ELISA法测定IL一1β、TNF-α的含量。
结果
1、临床研究
(1)两组患者治疗后心绞痛疗效分析：治疗4周后,治疗组患者中显效24例,改善13例,无效3例；对照组治疗4周后显效17例,改善15例,无效8例,总有效率比较治疗组总有效率为92%,对照组为80%,两组相比有显著统计学意义见(P<0.05)。
(2)两组患者治疗前后心绞痛发作情况对比：治疗组在治疗前心绞痛发作频率为(12.60±2.17)次／周,心绞痛发作持续时间(9.50±1.72)分／次,对照组心绞痛发作频率为(13.90±2.60)次／周,心绞痛发作持续时间(9.10±2.13)分／次,两组相比无显著差异(P>0.05),具有可比性。治疗4周后,治疗组发作频率(4.00±1.41)次／周,持续时间(3.90±1.29)分／次,对照组为(5.70±1.42)次／周,持续时间(5.20±1.32)分／次,两组心绞痛发作频率以及持续时间较治疗前均有显著降低,但治疗组降低更明显,组间比较有统计学意义(P<0.05)。
(3)两组患者接受治疗期间心血管事件发生次数比较：接受治疗干预期间,治疗组的心血管事件事件发生次数比对照组的发生次数明显要少,但主要是一般心血管事件事件的差异,而严重心血管事件(不包括终末事件如患者死亡)两组发生次数无明显差异。
(4)两组患者治疗前后中医临床症状积分比较：治疗前在症状积分方面,治疗组与对照组比较差异无统计学意义(P>0.05)；治疗后症状积分差值,治疗组高于对照组组,差异有显著性统计学意义(P<0.01)；治疗前后症状积分比较,二组治疗后均较治疗前降低,差异有显著性统计学意义(P<0.01)。(5)两组患者APACHEⅡ评分比较：入院时治疗组APACHE II评分平均为(15.10±3.47)分,对照组APACHEⅡ评分平均为(14..50±3.95)分,两组评分无显著差异(P>005)。纳入本研究的两组患者在疗程2周时各项主要疗效指标治疗组与对照组比较无显著性异(P>0 05),但和入院时评分比较有显著性差异(P<0 05)；在治疗4周时,两组评分都呈下降趋势,但治疗组组下降更明显,治疗组与对照组比较有显著差异(P<0.05)。
(6)两组硝酸甘油停减情况：治疗后对照组与治疗组相比无明显统计学意义(P>005)。
2、实验室指标分析：
(1)两组患者治疗前后心电图变化：治疗组干预四周后显效13例,改善16例,无效11例,对照组显效14例,有效18例,无效8例,两组比较无显著性统计学差异(P>0.05)。
(2)两组治疗前后血脂变化比较：完成本研究的两组患者治疗后血脂较治疗前均有明显改善,具体表现在TC、TG、LDL-C降低,HDL-C升高,但治疗组和对照组相比,治疗组血脂改善幅度更加明显,组间比较有统计学意义(P<0.05)。(3)两组治疗前后超敏CRP (hs-CRP)变化：治疗前两组hs-CRP(单位：mg／1)T值：0.207,P值=0.838>0.05,两组比较无统计学意义,具有可比性。治疗后两组hs-CRP值较治疗前均有明显降低,但治疗组降低更加明显,组间比较有有统计学意义(P<0.05)。
(4)治疗前后白细胞计数比较：治疗前两组WBC计数比较无统计学意义,具有可比性。治疗后两组WBC均有明显降低,但治疗组下降更明显,组间比较具有统计学意义(P<0.05)。两组治疗前后差值比较无统计学意义(P>0.05)。
(5)两组治疗前后纤维蛋白原(FIB)变化情况：两组治疗后FIB均较治疗前有明显降低,差异有统计学意义(P<0.05),但组间比较无明显统计学意义(P>0.05)
(6)两组治疗前后IL-1,TNF-a、SCD40L及MMP-9的变化：经统计分析,两组患者治疗前血中IL-1、TNF-a、SCD40L及MMP-9各项指标比较,差异无显著性意义(P>0.05)；治疗后组间比较治疗组各项指标均低于对照组(P<0.05)。其中治疗4周后,对照组血清MMP-9较治疗前略有下降,但均无显著性差异,治疗组MMP-9水平不但较治疗前有显著下降(P<0.01),两且较对照组亦有显著下降(P<0.01),说明治疗组在改善患者炎症指标方面优于对照组。
3.安全性评价：治疗前后,对接受本研究的80例患者行血、尿、大便常规及肝、肾功能等检查,其中对照组治疗后4周有1例患者出现ALT轻度升高,经予以护肝药口服,1月后复查肝功正常,1例患者出现轻度血色素下降,未予特殊处理；治疗组5例出现恶心、纳差等胃肠道不适症状未予特殊处理。实验中未发现其他患者肝肾功能异常等情况。
4、实验研究：大鼠垂体后叶素造模心肌缺血模型结果提示在心电图变化情况比较上,解毒活血汤高剂量组可改善垂体后叶素引起的心肌缺血,与模型组相比差异有显著性(P<0.05),低剂量显示改善倾向,但无统计学差异；各组大鼠实验室检测指标变化情况上,模型组心酶指标明显高于空白对照组,而解毒活血汤低、中及高剂量组可以显著改善心肌酶CK、LDH,在高剂量组尤其明显,有显著统计学意义(P<0.01)；血清lL-1β、TNF-α检测结果,模型组血清1L-1β、TNF-α明显高于空白对照组,而解毒活血汤低、中及高剂量组可以显著降低该两项指标,在高剂量组此种作用尤其明显,有显著统计学意义(P<0.01)。
结论
(1)应用解毒活血法治疗ACS在改善患者临床症状及症候分级量化上均有一定作用,能很好的控制病情,疗效优于单纯西药治疗组；(2)解毒活血法在改善ACS患者的实验室指标方面与对照组相比均有显著性差异,提示可能通过调节血脂和降低血清炎症因子水平、改善内皮功能等途径起到抗炎和抗动脉粥样硬化的作用；(3)动物垂体后叶素心肌缺血模型显示解毒活血法能明显改善心肌缺血,降低血清IL—1、TNF—α等促炎因子水平,在高剂量组这种作用尤为明显,为解毒活血法取得的临床疗效提供了充分的实验依据支持。
background
The basic pathogenesis of Acute Coronary Syndrome (ACS) was pyretic toxicity and blood stasis.according to the Professor chenjinghe's theory of acute coronary syndrome, who is famous in the first hospital affiliated to Guangzhou university of Chinese Medicine, as well as a number of clinical studies has shown in recent years. The detoxicating and promoting blood circulation therapy plays an important role in the the treatment of ACS by alleviating the body's inflammatory response in a certain degree, regulating lipid metabolism, enhancing the body resistance to hypoxia and anti apoptosis,r educing cardiomyocyte apoptosis, so as to improve the quality of life in the patients with ACS.
Objective
To objectively assess the clinical efficacy and safety of the detoxicating and promoting blood circulation therapy after 1 month treatmen and it's mechanism, thereby make an objective evaluation for the efficacy of Chinese medicine;as far as the experiment was concerned, the ecectrocardiograph(ECG) was observed in myocardial ischemia rats induced by pituitrin(Pit) through lingual vein, the contents of CK, LDH, IL-1β、TNF-αin serum was assayed respectively,in myocardial ischemia mice which pituitrin was peritoneal injected. the control group was established, for the purpose of definiting this method's effect (the detoxicating and promoting blood circulation therapy) in the treatment of ACS, so as to provide powerful experimental evidence for the clinical treatment.
Method:
80 cases with Acute coronary syndrome were collected and randomly divided into treatment and control groups, the control group was treated with Standard treatment method of Western medicine, while the treatment group was treated with standard Western medicine methos and the detoxicating and promoting blood circulation decoction. Therapeutic effect was evaluated according to the standard by Assessment on electrocardiograph(ECG), nitroglycerin consumption, symptom effect of Chinese Medicine, laboratory indicators of inflammation, Liver and kidney function before and after 4 weeks treatment between the two groups, analyze the correlative laboratory parameters such as the IL-1、TNF-a、SCD40L, MMP-9 in serum through statistical analysis so as to explore the mechanism, The side effect, The incidence rate of main cardiovascular lesion in the patients during treatment were recorded as well.the animal experiment research:the ecectrocardiograph(ECG) was observed inmyocardial ischemia rats induced by pituitrin(Pit) through lingual vein and intervened by the detoxicating and promoting blood circulation in high, medium and low dose (32g、16g、8g/kg) the contents of CK, LDH, IL-1β、TNF-αin serum was assayed respectively, in myocardial ischemia mice which pituitrin was peritoneal injected. subjects. sCD40L and TNF-a levels were measured by Enzyme-linked immunosorbent assay.
Result
(1)clinical therapeutic efect analysis of angina pectoris after treatment in the two groups:24 cases markedly effective, improved in 13 cases,3 cases invalid after four weeks intervention in the treatment group, the total effective percentage was 92%. while the cases was 17,15,8 rspectively in the control group, and the total effective percentage was 80%, there was distinct significance between the two group (P<0.05)
(2)Angina onset conparison before and after treatment between the two groups:the frequency and duration of angina attacks in the treated group before intervention was (12.60±2.17) times/week, (9.50±1.72) minutes /time,while it was (13.90±2.60) times/week, (9.10±2.13) minutes/time respectively in the control group, there was no significant difference between the two group (P>0.05). the frequency and duration of angina attacks in the treatment group after intervention was (4.00±1.41) times/week, (3.90±1.29) minutes/time, while in the control group it was (5.70±1.42) times/week, (5.20 ±1.32) minutes/time, There was obvious improvement in the two group, but the decrease margin in the treated group was more significant than that of the controlled group(p<0.05).
(3)The incidence rate of main cardiovascular events:compared with the control group, the times of cardiac incidents of the treated group was much less, but the difference comes from the times of common cardiac incidents, in terms of the times of serious cardiac incidents, there was no significant difference between the two group.
(4)The syndromes score of TCM:after being treated,the scores of clinical symptoms of the patients in two groups were reduced much and the clinical symptoms of two groups were improved effectively, when compared with the controlled group, the reduction of the scores of clinical symptoms in the treated group was more significant(P<0.01).
(5)the acute physiological and chronic healthy evaluationⅡ(APACHEⅡ) scores between the two group:the APACHEⅡscore was (15.10±3.47) in the treatment group, and it was (14..50±3.95) in the control group, there was no significant difference between the two group before intervention and after 2 weeks treatment, but the significance was obvious when compared with admission.- There was apparent improvement in the two group after 4 weeks treatment, but the improvement in the treated group was more significant than that of the controlled group(p<0.05).
(6)Nitroglgcerin withdrawal in the two group:there was no statistical significance between them after treatment (P>0.05)
2. laboratory test analysis
(1)The electrocardiograph(ECG) changes after treatment:13 cases markedly effective, improved in 16 cases,11 cases invalid after four weeks intervention in the treatment group, while The cases was 14,18,8 rspectively in the control group. there wase no obvious significance between the two group (P>0.05).
(2)The lipid level before and after the treatment:after the treatment, the lipid level of each group was both improved than that of the before, Such as the total cholesterol, total triglyceride, low density lipoprotein declined and high density lipoprotein rised. however, the improvement extent of the lipid level in the treated group was more significant than that of the controlled group(p<0.05).
(3)The level of hypersensitive C-reactive protein(hs-CRP):after the treaatment, the level of hs-CRP of each group was both lower than that of the before(p<0.01), but the decrease margin of the hs-CRP level in the treated group was more significant than that of the controlled group, (p<0.05).
(4)The level of leukocytes after treatment:there were no significance between the two group before treatment(P>0.05), while the difference were obvious after treatment between the two group(P<0.05) although the WBC count obviously declined in the control group. The difference value before and after treatment showed no statistically significant difference.
(5)The level of fibrinogen(FIB):there were obvious decline after treatment in the two group(P<0.05), while difference between two group showed no significant difference (P>0.05)
(6)Changes and relations betwvee IL-1, TNF-a、SCD40L and MMP-9 in patients of ACS after 4 weeks treatment:there was no statistical significance(P>0.05) between the two group before treatment, while the Serum IL-1, TNF-a、SCD40L and MMP-9 level was obviously lower in the treatment group than in control group after treatment((P<0.05). there was no significant difference in the level of MMP-9 before and after treatment in the control group, however the level of MMP-9 was obviously declined in the treatment group after treatment, and the difference was also visible between the two group. so the treatment group was superior to the control group in respect of inflammatory indicators improvement.
3. Observation of adverse reactions:1 patient had slightly elevated ALT and one case with slight low hemoglobin were observed in the control group after 4 weeks treatment,and the former's liver function got right 1 month later after took hepatinica orally,no special treatment measures was adopted for the latter.5 cases with nausea, poor appetite in the treatment group, other patients had no adverse reactions after treatment.
4. experimental study:the ecectrocardiograph(ECG) changes in myocardial ischemia rats induced by pituitrin(Pit) through lingual vein and intervened by the detoxicating and promoting blood circulation in high, medium and low dose shows high-dose group could improve pituitrin-induced myocardial ischemia much better than the model group (P<0.05), Low dose group showed improvement, but without significant difference.in terms of the changes in laboratory parameters, the cardiac enzyme, IL-1β、TNF-αwas much higher in the model group than the blank control group, and the low, middle and high dose group could improve cardiac enzyme and IL-1β、TNF-αin serum significantly, this change was particularly evident in the high dose group (P<0.01).
Conclusion
(1) The detoxicating and promoting blood circulation therapy had much better curative effect than the simple western medicine group for the ACS paients, particularly for the improvement in clinical symptoms. This therapy was safe and reliable, with no obvious toxicity;
(2) For the treated group,there was an obvious improvement in their laboratory parameters than the control group;
(3) the myocardial ischemia rats model induced by pituitrin(Pit) through lingual vein shows the detoxicating and promoting blood circulation therapy had a marked improvement in myocardial ischemia, reduction of serum IL-1, TNF-αpro-inflammatory cytokines, The clinical efficacy of Chinese medicine in curing ACS had to be further support by high-quality experimental trials. The suppression on the inflaumatory reaction of ACS may be one mechanism of TCM in treating patients with ACS.
毒壅血瘀为急性冠脉综合征的基本病机所在,根据导师多年临床经验及复习近年来多项临床研究显示,解毒活血法可不同程度地减轻机体的炎症反应,调节脂质代谢,提高机体抗缺氧能力和抗细胞凋亡的作用,减轻心肌细胞凋亡,提高患者生存质量。
目的
评价解毒活血法治疗急性冠脉综合征1个月后临床疗效和安全性,旨在初步观察解毒活血法干预急性冠脉综合征患者的临床疗效及作用机制,并对中医药的疗效作出客观评价；实验方面,采用大鼠垂体后叶素造模心肌缺血动物模型,以解毒活血法进行干预,并设立对照组,进一步明确解毒活血法在急性冠脉综合征中的治疗作用,从而为临床的治疗效果提供更有力的实验证据。
方法
对符合本研究纳入条件的80例急性冠脉综合征患者随机分为治疗组和对照组,对照组予以西医规范化治疗,治疗组在西医规范化处理基础上加用解毒活血汤进行干预。在严格按照临床研究设计的基础上,对纳入两组患者进行组间比较及治疗前后比较,通过分析治疗前后疗效指标、中医证候疗效指标、主要疗效指标、实验室炎症指标及肝肾功能等情况的变化,进行治疗前后的比较,安全性指标及不良反应、实验室检查和心电图等。进而分析治疗前后实验室指标及血清IL-1、TNF-a、SCD40L及MMP-9等相关资料的变化关系,通过统计学分析、探讨解毒活血法对急性冠脉综合征患者作用的机制所在。动物实验方法：以大鼠垂体后叶素造模心肌缺血为动物模型,以心酶、心电图及炎症介质标志物IL-1、TNF-a作为观察指标,观察解毒活血汤高、中、低剂量组(32g、16g、8g/kg)的治疗效果,采用ELISA法测定IL一1β、TNF-α的含量。
结果
1、临床研究
(1)两组患者治疗后心绞痛疗效分析：治疗4周后,治疗组患者中显效24例,改善13例,无效3例；对照组治疗4周后显效17例,改善15例,无效8例,总有效率比较治疗组总有效率为92%,对照组为80%,两组相比有显著统计学意义见(P<0.05)。
(2)两组患者治疗前后心绞痛发作情况对比：治疗组在治疗前心绞痛发作频率为(12.60±2.17)次／周,心绞痛发作持续时间(9.50±1.72)分／次,对照组心绞痛发作频率为(13.90±2.60)次／周,心绞痛发作持续时间(9.10±2.13)分／次,两组相比无显著差异(P>0.05),具有可比性。治疗4周后,治疗组发作频率(4.00±1.41)次／周,持续时间(3.90±1.29)分／次,对照组为(5.70±1.42)次／周,持续时间(5.20±1.32)分／次,两组心绞痛发作频率以及持续时间较治疗前均有显著降低,但治疗组降低更明显,组间比较有统计学意义(P<0.05)。
(3)两组患者接受治疗期间心血管事件发生次数比较：接受治疗干预期间,治疗组的心血管事件事件发生次数比对照组的发生次数明显要少,但主要是一般心血管事件事件的差异,而严重心血管事件(不包括终末事件如患者死亡)两组发生次数无明显差异。
(4)两组患者治疗前后中医临床症状积分比较：治疗前在症状积分方面,治疗组与对照组比较差异无统计学意义(P>0.05)；治疗后症状积分差值,治疗组高于对照组组,差异有显著性统计学意义(P<0.01)；治疗前后症状积分比较,二组治疗后均较治疗前降低,差异有显著性统计学意义(P<0.01)。(5)两组患者APACHEⅡ评分比较：入院时治疗组APACHE II评分平均为(15.10±3.47)分,对照组APACHEⅡ评分平均为(14..50±3.95)分,两组评分无显著差异(P>005)。纳入本研究的两组患者在疗程2周时各项主要疗效指标治疗组与对照组比较无显著性异(P>0 05),但和入院时评分比较有显著性差异(P<0 05)；在治疗4周时,两组评分都呈下降趋势,但治疗组组下降更明显,治疗组与对照组比较有显著差异(P<0.05)。
(6)两组硝酸甘油停减情况：治疗后对照组与治疗组相比无明显统计学意义(P>005)。
2、实验室指标分析：
(1)两组患者治疗前后心电图变化：治疗组干预四周后显效13例,改善16例,无效11例,对照组显效14例,有效18例,无效8例,两组比较无显著性统计学差异(P>0.05)。
(2)两组治疗前后血脂变化比较：完成本研究的两组患者治疗后血脂较治疗前均有明显改善,具体表现在TC、TG、LDL-C降低,HDL-C升高,但治疗组和对照组相比,治疗组血脂改善幅度更加明显,组间比较有统计学意义(P<0.05)。(3)两组治疗前后超敏CRP (hs-CRP)变化：治疗前两组hs-CRP(单位：mg／1)T值：0.207,P值=0.838>0.05,两组比较无统计学意义,具有可比性。治疗后两组hs-CRP值较治疗前均有明显降低,但治疗组降低更加明显,组间比较有有统计学意义(P<0.05)。
(4)治疗前后白细胞计数比较：治疗前两组WBC计数比较无统计学意义,具有可比性。治疗后两组WBC均有明显降低,但治疗组下降更明显,组间比较具有统计学意义(P<0.05)。两组治疗前后差值比较无统计学意义(P>0.05)。
(5)两组治疗前后纤维蛋白原(FIB)变化情况：两组治疗后FIB均较治疗前有明显降低,差异有统计学意义(P<0.05),但组间比较无明显统计学意义(P>0.05)
(6)两组治疗前后IL-1,TNF-a、SCD40L及MMP-9的变化：经统计分析,两组患者治疗前血中IL-1、TNF-a、SCD40L及MMP-9各项指标比较,差异无显著性意义(P>0.05)；治疗后组间比较治疗组各项指标均低于对照组(P<0.05)。其中治疗4周后,对照组血清MMP-9较治疗前略有下降,但均无显著性差异,治疗组MMP-9水平不但较治疗前有显著下降(P<0.01),两且较对照组亦有显著下降(P<0.01),说明治疗组在改善患者炎症指标方面优于对照组。
3.安全性评价：治疗前后,对接受本研究的80例患者行血、尿、大便常规及肝、肾功能等检查,其中对照组治疗后4周有1例患者出现ALT轻度升高,经予以护肝药口服,1月后复查肝功正常,1例患者出现轻度血色素下降,未予特殊处理；治疗组5例出现恶心、纳差等胃肠道不适症状未予特殊处理。实验中未发现其他患者肝肾功能异常等情况。
4、实验研究：大鼠垂体后叶素造模心肌缺血模型结果提示在心电图变化情况比较上,解毒活血汤高剂量组可改善垂体后叶素引起的心肌缺血,与模型组相比差异有显著性(P<0.05),低剂量显示改善倾向,但无统计学差异；各组大鼠实验室检测指标变化情况上,模型组心酶指标明显高于空白对照组,而解毒活血汤低、中及高剂量组可以显著改善心肌酶CK、LDH,在高剂量组尤其明显,有显著统计学意义(P<0.01)；血清lL-1β、TNF-α检测结果,模型组血清1L-1β、TNF-α明显高于空白对照组,而解毒活血汤低、中及高剂量组可以显著降低该两项指标,在高剂量组此种作用尤其明显,有显著统计学意义(P<0.01)。
结论
(1)应用解毒活血法治疗ACS在改善患者临床症状及症候分级量化上均有一定作用,能很好的控制病情,疗效优于单纯西药治疗组；(2)解毒活血法在改善ACS患者的实验室指标方面与对照组相比均有显著性差异,提示可能通过调节血脂和降低血清炎症因子水平、改善内皮功能等途径起到抗炎和抗动脉粥样硬化的作用；(3)动物垂体后叶素心肌缺血模型显示解毒活血法能明显改善心肌缺血,降低血清IL—1、TNF—α等促炎因子水平,在高剂量组这种作用尤为明显,为解毒活血法取得的临床疗效提供了充分的实验依据支持。
background
The basic pathogenesis of Acute Coronary Syndrome (ACS) was pyretic toxicity and blood stasis.according to the Professor chenjinghe's theory of acute coronary syndrome, who is famous in the first hospital affiliated to Guangzhou university of Chinese Medicine, as well as a number of clinical studies has shown in recent years. The detoxicating and promoting blood circulation therapy plays an important role in the the treatment of ACS by alleviating the body's inflammatory response in a certain degree, regulating lipid metabolism, enhancing the body resistance to hypoxia and anti apoptosis,r educing cardiomyocyte apoptosis, so as to improve the quality of life in the patients with ACS.
Objective
To objectively assess the clinical efficacy and safety of the detoxicating and promoting blood circulation therapy after 1 month treatmen and it's mechanism, thereby make an objective evaluation for the efficacy of Chinese medicine;as far as the experiment was concerned, the ecectrocardiograph(ECG) was observed in myocardial ischemia rats induced by pituitrin(Pit) through lingual vein, the contents of CK, LDH, IL-1β、TNF-αin serum was assayed respectively,in myocardial ischemia mice which pituitrin was peritoneal injected. the control group was established, for the purpose of definiting this method's effect (the detoxicating and promoting blood circulation therapy) in the treatment of ACS, so as to provide powerful experimental evidence for the clinical treatment.
Method:
80 cases with Acute coronary syndrome were collected and randomly divided into treatment and control groups, the control group was treated with Standard treatment method of Western medicine, while the treatment group was treated with standard Western medicine methos and the detoxicating and promoting blood circulation decoction. Therapeutic effect was evaluated according to the standard by Assessment on electrocardiograph(ECG), nitroglycerin consumption, symptom effect of Chinese Medicine, laboratory indicators of inflammation, Liver and kidney function before and after 4 weeks treatment between the two groups, analyze the correlative laboratory parameters such as the IL-1、TNF-a、SCD40L, MMP-9 in serum through statistical analysis so as to explore the mechanism, The side effect, The incidence rate of main cardiovascular lesion in the patients during treatment were recorded as well.the animal experiment research:the ecectrocardiograph(ECG) was observed inmyocardial ischemia rats induced by pituitrin(Pit) through lingual vein and intervened by the detoxicating and promoting blood circulation in high, medium and low dose (32g、16g、8g/kg) the contents of CK, LDH, IL-1β、TNF-αin serum was assayed respectively, in myocardial ischemia mice which pituitrin was peritoneal injected. subjects. sCD40L and TNF-a levels were measured by Enzyme-linked immunosorbent assay.
Result
(1)clinical therapeutic efect analysis of angina pectoris after treatment in the two groups:24 cases markedly effective, improved in 13 cases,3 cases invalid after four weeks intervention in the treatment group, the total effective percentage was 92%. while the cases was 17,15,8 rspectively in the control group, and the total effective percentage was 80%, there was distinct significance between the two group (P<0.05)
(2)Angina onset conparison before and after treatment between the two groups:the frequency and duration of angina attacks in the treated group before intervention was (12.60±2.17) times/week, (9.50±1.72) minutes /time,while it was (13.90±2.60) times/week, (9.10±2.13) minutes/time respectively in the control group, there was no significant difference between the two group (P>0.05). the frequency and duration of angina attacks in the treatment group after intervention was (4.00±1.41) times/week, (3.90±1.29) minutes/time, while in the control group it was (5.70±1.42) times/week, (5.20 ±1.32) minutes/time, There was obvious improvement in the two group, but the decrease margin in the treated group was more significant than that of the controlled group(p<0.05).
(3)The incidence rate of main cardiovascular events:compared with the control group, the times of cardiac incidents of the treated group was much less, but the difference comes from the times of common cardiac incidents, in terms of the times of serious cardiac incidents, there was no significant difference between the two group.
(4)The syndromes score of TCM:after being treated,the scores of clinical symptoms of the patients in two groups were reduced much and the clinical symptoms of two groups were improved effectively, when compared with the controlled group, the reduction of the scores of clinical symptoms in the treated group was more significant(P<0.01).
(5)the acute physiological and chronic healthy evaluationⅡ(APACHEⅡ) scores between the two group:the APACHEⅡscore was (15.10±3.47) in the treatment group, and it was (14..50±3.95) in the control group, there was no significant difference between the two group before intervention and after 2 weeks treatment, but the significance was obvious when compared with admission.- There was apparent improvement in the two group after 4 weeks treatment, but the improvement in the treated group was more significant than that of the controlled group(p<0.05).
(6)Nitroglgcerin withdrawal in the two group:there was no statistical significance between them after treatment (P>0.05)
2. laboratory test analysis
(1)The electrocardiograph(ECG) changes after treatment:13 cases markedly effective, improved in 16 cases,11 cases invalid after four weeks intervention in the treatment group, while The cases was 14,18,8 rspectively in the control group. there wase no obvious significance between the two group (P>0.05).
(2)The lipid level before and after the treatment:after the treatment, the lipid level of each group was both improved than that of the before, Such as the total cholesterol, total triglyceride, low density lipoprotein declined and high density lipoprotein rised. however, the improvement extent of the lipid level in the treated group was more significant than that of the controlled group(p<0.05).
(3)The level of hypersensitive C-reactive protein(hs-CRP):after the treaatment, the level of hs-CRP of each group was both lower than that of the before(p<0.01), but the decrease margin of the hs-CRP level in the treated group was more significant than that of the controlled group, (p<0.05).
(4)The level of leukocytes after treatment:there were no significance between the two group before treatment(P>0.05), while the difference were obvious after treatment between the two group(P<0.05) although the WBC count obviously declined in the control group. The difference value before and after treatment showed no statistically significant difference.
(5)The level of fibrinogen(FIB):there were obvious decline after treatment in the two group(P<0.05), while difference between two group showed no significant difference (P>0.05)
(6)Changes and relations betwvee IL-1, TNF-a、SCD40L and MMP-9 in patients of ACS after 4 weeks treatment:there was no statistical significance(P>0.05) between the two group before treatment, while the Serum IL-1, TNF-a、SCD40L and MMP-9 level was obviously lower in the treatment group than in control group after treatment((P<0.05). there was no significant difference in the level of MMP-9 before and after treatment in the control group, however the level of MMP-9 was obviously declined in the treatment group after treatment, and the difference was also visible between the two group. so the treatment group was superior to the control group in respect of inflammatory indicators improvement.
3. Observation of adverse reactions:1 patient had slightly elevated ALT and one case with slight low hemoglobin were observed in the control group after 4 weeks treatment,and the former's liver function got right 1 month later after took hepatinica orally,no special treatment measures was adopted for the latter.5 cases with nausea, poor appetite in the treatment group, other patients had no adverse reactions after treatment.
4. experimental study:the ecectrocardiograph(ECG) changes in myocardial ischemia rats induced by pituitrin(Pit) through lingual vein and intervened by the detoxicating and promoting blood circulation in high, medium and low dose shows high-dose group could improve pituitrin-induced myocardial ischemia much better than the model group (P<0.05), Low dose group showed improvement, but without significant difference.in terms of the changes in laboratory parameters, the cardiac enzyme, IL-1β、TNF-αwas much higher in the model group than the blank control group, and the low, middle and high dose group could improve cardiac enzyme and IL-1β、TNF-αin serum significantly, this change was particularly evident in the high dose group (P<0.01).
Conclusion
(1) The detoxicating and promoting blood circulation therapy had much better curative effect than the simple western medicine group for the ACS paients, particularly for the improvement in clinical symptoms. This therapy was safe and reliable, with no obvious toxicity;
(2) For the treated group,there was an obvious improvement in their laboratory parameters than the control group;
(3) the myocardial ischemia rats model induced by pituitrin(Pit) through lingual vein shows the detoxicating and promoting blood circulation therapy had a marked improvement in myocardial ischemia, reduction of serum IL-1, TNF-αpro-inflammatory cytokines, The clinical efficacy of Chinese medicine in curing ACS had to be further support by high-quality experimental trials. The suppression on the inflaumatory reaction of ACS may be one mechanism of TCM in treating patients with ACS.
引文
[1]陈可冀,史载祥.凋亡因子在冠心病中的作用及活血化瘀药对其干预的影响.中国中医基础医学杂志,2008；14(4)：280-282.
[2]黄衍寿,莫鸿辉,洪永敦,等.清热解毒法治疗急性冠脉综合征55例.广州中医药大学学报,2006；23(1)：13-16.
[3]吴伟,彭锐.冠心病热毒病机的探讨.新中医,2007；39(6)：3-4.
[4]丁书文,李晓,李运伦.热毒学说在心系疾病中的构建与应用.山东中医药大学学报,2004；28(6)：413-416.
[5]于涛,曹洪欣.胸痹(冠心病)病机演变探微.中医药信息,2004；21(2)：1-2.
[6]高宪玺,冯伟.略论胸痹心痛的中医病机.河北中医,2008；30(8)：864-865.
[7]李爱民.冠心病从络论治浅议.现代中西医结合杂志,2005；14(16)2116-2117.
[8]范逸品,宋雨婷,梁跃,等.从络论治冠心病心绞痛用药规律初探.北京中医药大学学报,2009；32(6)：386-388.
[9]伍世林.冠心病从“络”论治探讨.浙江中医杂志,2006；41(10)：584.
[10]屈松柏,李家庚.实用中医心血管病学.北京：科技文献出版社,1993.35
[11]于德洵,于德伟.胸痹心痛与五脏相关治则之探讨.吉林中医药,2005；25(4)：10
[12]庞敏,于跃飞.胸痹心痛与五脏的关系浅论.实用中医内科杂志,2005；19(3)：195.
[13]刘超峰,范虹.名老中医雷忠义治疗冠心病心绞痛痰瘀互结证的经验.陕西中医,2003：23(8)：722-723.
[14]张京春,陈可冀,张文高,等.不稳定斑块的中西医结合认识现状及研究思路.中国中西医结合杂志,2005；25(10)：869-871.
[15]张蕴慧.周次清教授“急则治本”论治急性心肌梗死经验.山东中医药大学学报,2006：30(3)：215-217.
[16]陈全福,刘敏雯.急性冠脉综合征与中医“风”的关系.辽宁中医学院学报,2004：6(6)：457-458.
[17]金华,金钊,张蕾蕾.从炎症发病机制探讨急性冠脉综合征的中医治法.中国中医基础医学杂志,2006：12(10)：752-754,764.
[18]吴以岭.中医络病学说与三维立体网络系统.中医杂志,2003；44(6)：407-409.
[19]杨广,张敏州.邓铁涛教授治疗急性心肌梗死冠脉介入术后验案举隅.实用中医内科杂志,2005；19(5)：415.
[20]吴伟康,邓铁涛.邓老“痰瘀相关”理论与冠心病防治.深圳中西医结合 杂,2006：16(1)：13-16,20.
[21]邢丽,李鑫.辩证分型治疗冠心病心绞痛浅识.实用中医内科杂志,2007；21(5)：39.
[22]其其格,王伟,胡立,等.9790例冠心病心绞痛辨证分型文献统计分析.山西中医,2008：24(10)：31-33.
[23]郭志华.冠心病心绞痛2432例中医辨证分型综合统计分析.湖南中医杂志,1998：14(2)：7-8.
[24]吴辉,于扬文,吴伟,等.116例冠心病患者中医证候及病因分析.江苏中医药,2004；25(10)：30-31.
[25]郑筱萸主编.中药新药临床研究指导原则.北京,中国医药科技出版社.2002年版.
[26]王先敏,李鹏,阿娜尔汗.冠心病从痰瘀论治的客观基础与机制探析.实用中医内科杂志.2006；20(2)：124.
[27]方显明,黄红英.冠心病心绞痛从痰论治探讨.广西中医药,2001；24(1)：42-43.
[28]靳华.浅谈冠心病从痰瘀分型论治.光明中医,2009；24(9)：1787-1788.
[29]韩丽华,吴鸿,吕翠田,等.宽胸丹治疗痰瘀阻滞型胸痹(冠心病心绞痛)临床观察.河南中医.2005：25(1)：35-37.
[30]张效科,马松涛,杨磊,等.冠心病从肾论治的理论依据及意义.四川中医,2004：22(4)：18-19.
[31]张晓星,龚恬,张立平.冠心病从肾论治.新中医,2008；40(5)：3-4.
[32]鲁厚年.补肾化瘀法治疗冠心病心绞痛48例.中国现代医生,2009；47(2)：73-74.
[33]郑耀庭.浅谈从肝论治冠心病.中国中医基础医学杂志,2002；8(10)：40-41.
[34]周承志,唐娟.冠心病从肝论治五法.湖北中医杂志,2001；23(10)：19.
[35]胡贤琼.从肝论治冠心病心绞痛32例.四川中医,2004；22(1)：36-37
[36]苗阳,高铸烨.冠心病从风论治浅谈.庆祝中国中医研究院成立50周年首届中医药发展国际论坛暨首届中医药防治艾滋病国际研讨会论文,北京,2005：610-613.
[37]陈锋,王文文.再探冠心病从肺论治.现代中西医结合杂志,2002；11(6)：547.
[38]王霭平.从肺论治胸痹心痛的临床观察.上海针灸杂志,2004；23(4)：25.
[39]王香存.谈冠心病心绞痛从脾胃论治.河南中医学院学报,2005；20(3)： 44-45.
[40]李宁.从脾胃论治冠心病心绞痛72例.甘肃中医学院学报.2004,21(4)：32-33.
[41]戴瑞鸿.我与麝香保心丸.中国中西医结合杂志,2000；20(3)：243-244
[42]金椿,王受益,戴瑞鸿.麝香保心丸对16例冠心病心绞痛患者运动耐量的影响.上海医药,1997；18(5)：23-26.
[43]吕国庆,戴瑞鸿.顾家韵,等.麝香保心丸在不稳定性心绞痛治疗中的作用.中西医结合杂志,1987：7(7)：405-406.
[44]上海市麝香保心丸协作组.麝香保心丸治疗冠心病心绞痛的疗效观察.中成药研究.1984,6(3)：21-23.
[45]常以芳,韩瑞丰,韩海英,等.麝香保心丸与消心痛治疗冠心病的临床疗效观察.上海医药,1996：17(12)：12-13.
[46]沈玉芳,陈大年,王邦宁,等.麝香保心丸与消心痛患者冠心病心绞痛的对比性研究.上海医药,1996：17(12)：22-24.
[47]魏艳阳,周明银.麝香保心丸治疗冠心病不稳定型心绞痛临床观察.中国现代药物应用.2009,3(9)：14-15.
[48]王蕾,熊泽宇,王刚.复方丹参滴丸治疗稳定型心绞痛随机对照试验的系统评价[J].中国中西医结合杂志,2004；24(6)：500—504.
[49]张敏州,张俭.复方丹参滴丸治疗冠心病的Meta分析.时珍国医国药,2009；20(4)：1007—1008.
[50]陈焕清,熊小强,段朝晖,等.复方丹参滴丸对冠心病血管内皮功能的干预及其机制.中山大学学报(医学科学版),2009；30(4S)：221-223.
[51]殷建明,罗陆一,张大创,等.通心贴穴位外治冠心病心绞痛临床研究.中西医结合心脑血管病杂志,2009；7(10)：1138-1140.
[52]张明雪,常艳鹏,曹洪欣.温阳活血中药复方调控冠心病(心)阳虚血瘀证大鼠血小板内受体、信号转导的作用机制研究.中华中医药杂志.2008,23(6)：494-497.
[53]郑丽艳,张桂红,吴庆田,等.纳米中药心肌益生散对心肌细胞增殖的影响.黑龙江医药科学,2009；32(4)：18-19.
[54]张传清,施麟,黄建萍,等.安心颗粒治疗冠心病心绞痛实验研究.中国中医急症.2004,13(9)：613-614.
[55]Braunwald E, Mark DB, Jones RH, et al. Unstable angina:diagnosis and management. Rockvilles M D:Agency for Health Care Policy and Research and the National Heart, Lung, and Blood Institute, US Public Health Service, US Department of Health and Human Services:1994:1;Publication No 94-0602.
[56]王吉耀主编.内科学.北京：人民卫生出版社,2005年8月第一版.
[57]吴兆苏,姚崇华,赵冬,等.我国多省市心血管趋势决定因素的人群检测(中国MONICA方案)发病率和死亡率检测结果.中华心血管病杂志.1997；25(1)：6-11.
[58]Abdelmout I, DANCHIN N, ILARDO C, et al. C-reactive protein and coronary artery disease:Additional evidence of the implication of an inflammatory process in acute coronary syndromes. Am Heart J,1999,137(2): 346-351.
[59]Libby P, Ridker PM, Maseri A. Inflammation and atheroaclerosis. Circulation,2002,105:2092-2197.
[60]Hartford M, Wiklund 0, Mattsson-Hulen L, et al.C-reactive protein, interleukin-6, secretory phoSpholipase a group II A and intercdular adhesion moleculel in the prediction of late outcome events after acute Coronary syndromes. J Intern Med,2007,262(5):526-536.
[61]田学增.阿奇霉索干预急性冠脉综合征对其心脏不良事件再发生的影响.第二军医大学学报,2003；24(24)：772.
[62]曹建红.急性冠脉综合征与C一反应蛋白、尿酸、颈动脉内一中膜厚度的相关性分析.浙江临床医学,2009；11(4)：374-376.
[63]Pasterkamp G, Schoneveld AH, Hijnen DJ, et al. Atheroselemtic arterial remodeling and the localization of macrophages and matrix metalloproteases 1,2 and 9 in the human coronary artery [J]. Atherosclerosis, 2000,149(2):245-253.
[64]Lamberl E, Dasse E, Haye B。etal. TIMPs as multifacial proteins. Crit Rev Oncol Hematol,2004,149(3):187-198.
[65]Leu HB,Lin CP, Lin WT, etal.Circulating mononuelear superoxide production and inflammatory markers for long term prognosis in patients with cardiac syndrome X[J]. Free Radic Biol Med,2006; 40(6):983-91.
[66]Tai MH, Kuo SM, Liang liT, et aL Modulation of angiogenie processes in cultured endothelial cells by low density lipoproteim subfraetions from patients with familial hypercholesterolemia[J].Atherosclerosis,2006; 186(2): 448-57.
[67]赖泽仁,李凌,金焱.缺血修饰白蛋白在老年急性冠脉综合征诊断中的应用.中国老年学杂志,2007；27(13)：1267-1269.
[68]黄晓华,肖婷.急性冠脉综合征患者缺血修饰白蛋白的检测及临床应用.医学临床研究,2009；26(11)：2109-2111.
[69]Shmuel Schwartzenberg, Varda Deutsch, Sofia Maysel-Auslender, et al. Circulating Apoptotic Progenitor Cells:A Novel Biomarker in Patients With Acute Coronary Syndromes. Arterioscler Thromb Vasc Biol.2007,5:27-31.
[70]Brays Genis A, Conover CA, Overgaard MT, etal. Pregnancy associated plasma protein A as a marker of acute coronary syndromes[J]. N Engl J Med, 2001,345(14):1022-1029.
[71]Qin QP, Laitinen P, Majamaa-Voltti K, et al. Release patterns of pregnancy associated plasma protein A(PAPP-A)in patients with acute coronary syndromes [J]. Stand Cardiovasc J,2002,36(6):358-361.
[72]段樱,谭兵。刘树业.两种心脏标志物诊断急性冠脉综合征的对比研究.山东医药,2009,49(16)：90-91.
[73]刘荣静,习浩.急性冠脉综合征早期诊断中不同血清标记物组合的比较.循证医学,2009,9(5)：309-313.
[74]Kilcullen N, Viswanathan K, Das R, et al. Heart-type fatty acid binding protein predicts long term mortality after acute coronary syndrome and identifies high risk patients across the range of troponin values [J]. Journal of the American College of Cardiology.2007,50(21):2061-2067.
[75]Matsumura T, Saito T, Fujimura H, et al. Cardiac troponin 1 for accurate evaluation of cardiac Status in myopathic patients [J]. Brain and Development, 2007,29(8):496-501.
[76]陈晓园,彭鹏.心型脂肪酸结合蛋白对急性冠脉综合征的诊断价值.中国全科医学.2009,12(24)：2253-2254.
[77]Angiolillo DJ, Guzman LA. Clinical overview of promising nonthienopyridine antiplatelet agents[J], Am Heart J,2008,156(2 suppl): s23-s28.
[78]de Gaetano G, Donati MB, Cerietti C. Prevention of thrombosis and vascular infllammation:benefit and limitations of selective or combined COX-1. COX-2 and 5-LOX inhibitors[J]. Trends Phannacol Sci,2003,24(5): 245-252.
[79]Nicholas B Norgard, Mazen Abu-Fade. Comparison of prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Vascular Health and Risk Management 2009:5 873-882.
[80]MeCann CJ. Menown IB. New anticoagulant strategies in ST elevation myocardial infarction:trials and clinical implications [J]. Vasc Health Risk Mansg。2008,4(2):305-313.
[81]黄宏星.近期发布几项血栓抗凝药物临床应用中国专家共识介绍.中国医药 导刊.2009,11(10)：1638-1639.
[82]何川,燕纯伯.急性冠脉综合征抗凝治疗进展.心血管病学进展.2008,29(5)：764-767.
[83]杨新春.急性冠脉综合征抗凝与抗血小板治疗.医师进修杂志(内科版),2004：27(10)：6-9.
[84]Braunwald E et al. American College of ardiology (ACC)and the American Heart Association (AHA) Guidelines, USA:ACC/AHA; 2002.
[85]Koga H, Sugiyama S, Ogawa H. Acute coronary syndrome related factors[J]. Nippon Rinsho,2006; 64(4):642-6.
[86]Souza-Coata DC, Figueiredo-Lopes L, Alves-Fiiho JC, etal. Protective effects of atorvsstatin in rat models of acute pulmonary embolism:involvement of matrix metalloproteirmse-9 [J]. Crit Care Med.2007; 35(1):239-245.
[87]Libby P. Inflammation and Atherosclerosis[J]. Circulation,2002, 105(9):1135-1143.
[88]Olsson AG, Schwartz GG, Szarck M, et al. Effects of high-dose atorvastatin in patients>or=65 years of age with acute coronary syndrome (from the myocardial ischemia reduction with aggressive cholesterol lowering [MIRAC] study) [J]. Am J Cardiol.2007,99(5):632-635.
[89]刘甲兴,芮磊,洪原,等.急性冠脉综合征入院即刻应用辛伐他汀对炎症因子的影响.临床军医杂志.2009,37(4)：607-609.
[90]马风英,姚青海,吴尚勤,等.阿托伐他汀对急性冠脉综合征患者MMP9／TIMPl及预后的影响.天津医药.2009,37(8)：701-702
[91]艾德惠,蔡志友,陈和,等.急性冠脉综合征血清OX—LDL水平及阿托伐他汀的干预作用.中国老年学杂志.2009,29(15)：1958-1960.
[92]Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C reactive protein, and coronary artery disease N Engl J Med 2005; 352(1):29-38.
[93]Smith SC Jr., Feldman TE, Hirshfeld JW Jr, et al. ACC/AHA/SCAI 2005 guideline update for percutoneous coronary intervention a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol,2006,47:121.
[94]Antman EM, Hand M, Armstrong PW. et aL 2007 Focused Update of the ACC /AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction:A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol,2008, 51：210-247.
[95]周玉杰,杨士伟.急性冠脉综合征抗栓与溶栓治疗.临床药物治疗杂志,2009：7(3)：12-16.
[96]周延民,刘春,贺晓晶.急性冠脉综合征药物治疗进展.中国医学创新.2009,6(28)：186-187.
[97]高润霖.从急性心肌梗死治疗指南看再灌注治疗策略的选择.中华心血管病杂志,2005,33(11)1061-1064.
[98]From AM, Rihal CS, Lennon RJ, et al.Temporal trends and improved outcomes of percutaneous coronary revascularization in nonagenarians [J]. JACC Cardiovasc Inten,2008,1(6):692-698.
[98]Overbaugh KJ. Acute Coronary syndrome [J]. Am J Nurs,2009,109(5): 42-52.
[100]Chanwalit N, Yipintsoi T, Treankosol D, et al. Prognostic value of Selected presenting features of acute coronary syndrome in predicting inhospital adverse events:insight from the acute coronary syndrome registry[J]. Intern Med,2009,48(9):639-646.
[101]中华医学会心血管学分会.不稳定性心绞痛诊断和治疗建议[J].中华心血管病杂志,2000：28(6)：409—412.
[102]中华医学会心血管学分会.急性心肌梗死诊断和治疗指南[J].中华心血管病杂志,2001,29(12)：710—725.
[103]Antman et al.. ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction.2004 ACC/AHA Practice Guidelines.1-211.
[104]The task force on the management of ST- segment elevation acute Myocardial Infarction of the European Society of Cardiology. Management of acute Myocardial Infarction in patients presenting with persistent ST- segment elevation. European Heart Journal.2008(29):2909-2945.
[105]沈绍功,王承德,闫希军.中医心病诊断疗效标准与用药规范.北京,北京出版社,2002年2月第1版.
[106]吴伟康,候灿,罗汉川,等.垂体后叶素性心肌缺血模型再探[J].中国病理生理杂志.1993.9(2)：124.
[107]徐叔云.药理学实验方法第2版.北京：人民卫生出版社.1991,897.
[108]胡东裴,胸痹证治文献研究.山东中医药大学学报,2005；29(1)：37-40.
[109]方青,詹小萍,莫剑翎,等.黄连解毒汤对AD大鼠的治疗作用及对细胞因子含量的影响.中国中药杂志,2004；29(6)：575-578.
[110]Conti CR. Update pathophysiologic concepts in unstable coronary artery disease. Am Heart J,2001,141:S12.
[111]侯家玉.中药药理学.北京：中国中医药出版社,2002,39-66,202-242.
[112]王本祥.现代中药药理学.天津：天津科学技术出版社,1997：915,368.
[113]张京春,陈可冀,张文高,等.不稳定斑块的中西医结合认识现状及研究思路.中国中西医结合杂志,2005；25(10)：869-871.
[114]Wen C, Xu H, Huang QF, et al. Effect of drugs for promoting blood circulation on blood lipids and inflammatory reaction of atherosclerotic plaques in apoE gene deficiency mice. Chi J Integr Tradit West Med 2005: 25(4):345-349.
[115]吴辉,洪永敦,吴伟,等.冠心病痰热证候与炎症因子相关性探讨.辽宁中医杂志,2004；31(7)：52-543.
[116]黄衍寿,莫鸿辉,洪永敦,等.清热解毒法治疗急性冠脉综合征55例.广州中医药大学学报,2006；23(1)：13-16.
[117]陈可冀,史载祥.凋亡因子在冠心病中的作用及活血化瘀药对其干预的影响.中国中医基础医学杂志,2008；14(4)：280-282.
[118]李敏王硕仁赵明镜,等.活血益气方药对心肌梗死后心力衰竭大鼠心肌细胞凋亡的影响.中西医结合心脑血管杂志,2005；3(1)：33-35.
[119]常志文,刘琦.缺血再灌注心肌细胞凋亡及药物干预.中国新药杂志,2000；9(1)：28.
[120]李源段红王天成,等.川芎嗪对再灌注大鼠心肌细胞c-fos基因表达凋亡的影响.心脏杂志.2000,12(3)：213.
[121]赵明中,刘岚,汪家瑞,等.通心络胶囊对异丙肾上腺素致鼠心肌损伤保护作用的实验研究.中国中西医结合杂志,2001；21(1)：51.
[122]李锦山,李国辉,缪英年,等.川芎嗪抗大鼠心肌缺血及抗心细胞凋亡作用.中国实用医药,2008；3(32)：1-2.
[123]陈俊荣,陈俊红,王梅,等.酒大黄对动脉粥样硬化兔血脂水平的影响.中国医药导刊.2009：11(11)：1899-1900.
[124]朱郁文.浅析大黄的几种炮制方法及其影响.中医药导报,2007；13(8)：91-92
[125]侯改霞,杨建雄.连翘叶茶提取物对力竭运动及恢复期小鼠心肌抗氧化酶和LDH同工酶活性的影响.中国运动医学杂志.2006,25(1)：90-92
[126]梁日欣,廖福龙,韩东.川芎嗪预处理对麻醉家兔心肌缺血再灌注损伤的保护作用.中药药理与临床,2000,16(2)：11
[127]Kato T, Noguchi K, Sakanashi M, et al. Effects ofthe water extract of Chrysanthemum indicum Linn on coronary and systemic hemodynamics in the dog[J]Arch hat Phacmacodyn Ther,1986,280(2):241-253.
[128]陈铎葆,张雷,孙静文,等.红花水提物对心肌缺血大鼠的血液流变学与血小板聚集影响的实验研究.中国中医药科技,2004.11(5)：290.
[129]王艳春,张忠艳,姜小卓.中药黄芩的药理及应用.中外医疗.2009,28(13)：158
[130]莫晓燕,黄海霞,洪喻,等.赤芍总苷对培养乳鼠心肌细胞损伤的抗氧化作用.中国药理学通报,2004,20(10)：1119—1121.
[131]许春华,刘秀芝.急性冠脉综合征中医症型分布规律及临床观察.中外健康文摘,2009；8(12)：10-12.
[132]魏丹霞,刘明,庞永诚,等.111例冠心病患者中医证型分布规律研究.云南中医中药杂志,2008；29(7)：7-8.
[133]陈力,肖政.急性冠脉综合征中医证候回顾研究.广州中医药大学学报,2008；25(3)：248-250.
[134]李延芳.血府逐瘀汤治疗气滞血瘀型心绞痛30例.现代中医药,2008；28(2)：17-18.
[135]郑春松,黄钦,李旭东,等.血府逐瘀汤在心血管疾病方面的计算机药理学探讨.计算机与应用化学,2009；26(1)：9-16.
[136]王少英.清热解毒药物在治疗冠心病中的运用.北京中医杂志,2004；23(1)：14—15.
[137]钱卫东,陈晓虎.清热活血法干预急性冠脉综合征炎症反应的临床观察.湖北中医杂志,2010；32(1)：17-18.
[138]李娟,罗小星.建立中医危重病评分系统的初步探讨.中国中医急症,2009；18(6)：925-926。
[139]俞建华,刘新兵,方旭成,等.入院时APACHE—Ⅱ评分在急性心肌梗死患者危险分层中的应用价值.实用诊断与治疗杂志,2008；22(3)：163-164.
[140]汤日波,刘晓辉,谢莲娜,等.APACHEⅡ评分在急性冠脉综合征中的应用.中华急诊医学杂志,2005；14(8)：682-683.
[141]梅运清,季强,冯靖,等.冠状动脉旁路移植术后全身炎性反应综合征患者APACHEIII评分与炎症介质的相关性研究.中华医学杂志,2006；86(13)：927-929.
[142]顾伟,殷文朋,李春盛.肌钙蛋白Ⅰ和APACHE-Ⅱ评分在危重病患者预后中的应用价值[J].中国实用内科杂志,2007；27(17)：1373-1375.
[143]Knaus W A, Zinmerman J E。Wagner D P, et al. APACHEII:a severity of disease classification system[J]. Cirt Care Med,1983,13(10):818-826.
[144]speidl W S, Graf s, Hornykewycz S, et al. High sensitivity C-reactive protein in the prediction of coronary events in patients with premature coronary artery disease[J]. Am Heart J,2002,144(3):449.
[145]Yoshiya Monden, Toru Kubota, Takaki Tsutsumi, et al. Soluble TNF receptors prevent opoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction[J]. Cardiovascular Research,2007, 73(4):794-805.
[146]Mach F, Schonbeck U, bbby P. CD40 signaling in vascular cells:akeyrole in atherosclerosis. Atherosclerosis,1998,137(suppl):S89-S95.
[147]付瑜,姜树民.建立急性冠状动脉综合征动物模型的研究.中华中医药学刊,2007：25(1)：105-107.
[148]施新献.现代医学实用动物学.北京：人民军医出版社.2000：442—444.
[149]王洁,吕吉元,张明升,等.清醒无拘束大鼠心肌缺血模型的制备.山西医科大学学报,2007；38(5)：398-400.
[150]吴伟康,周琳,孙慧兰.四逆汤对心肌缺血大鼠心肌内皮素影响的实验研究.中国中西医结合杂志,2002；22(8)：610-612.
[151]吴伟康,侯灿,罗汉川,等.垂体后叶素性心肌缺血模型再探.中国病理生理杂志,1993：9(2)124-127.
[2]黄衍寿,莫鸿辉,洪永敦,等.清热解毒法治疗急性冠脉综合征55例.广州中医药大学学报,2006；23(1)：13-16.
[3]吴伟,彭锐.冠心病热毒病机的探讨.新中医,2007；39(6)：3-4.
[4]丁书文,李晓,李运伦.热毒学说在心系疾病中的构建与应用.山东中医药大学学报,2004；28(6)：413-416.
[5]于涛,曹洪欣.胸痹(冠心病)病机演变探微.中医药信息,2004；21(2)：1-2.
[6]高宪玺,冯伟.略论胸痹心痛的中医病机.河北中医,2008；30(8)：864-865.
[7]李爱民.冠心病从络论治浅议.现代中西医结合杂志,2005；14(16)2116-2117.
[8]范逸品,宋雨婷,梁跃,等.从络论治冠心病心绞痛用药规律初探.北京中医药大学学报,2009；32(6)：386-388.
[9]伍世林.冠心病从“络”论治探讨.浙江中医杂志,2006；41(10)：584.
[10]屈松柏,李家庚.实用中医心血管病学.北京：科技文献出版社,1993.35
[11]于德洵,于德伟.胸痹心痛与五脏相关治则之探讨.吉林中医药,2005；25(4)：10
[12]庞敏,于跃飞.胸痹心痛与五脏的关系浅论.实用中医内科杂志,2005；19(3)：195.
[13]刘超峰,范虹.名老中医雷忠义治疗冠心病心绞痛痰瘀互结证的经验.陕西中医,2003：23(8)：722-723.
[14]张京春,陈可冀,张文高,等.不稳定斑块的中西医结合认识现状及研究思路.中国中西医结合杂志,2005；25(10)：869-871.
[15]张蕴慧.周次清教授“急则治本”论治急性心肌梗死经验.山东中医药大学学报,2006：30(3)：215-217.
[16]陈全福,刘敏雯.急性冠脉综合征与中医“风”的关系.辽宁中医学院学报,2004：6(6)：457-458.
[17]金华,金钊,张蕾蕾.从炎症发病机制探讨急性冠脉综合征的中医治法.中国中医基础医学杂志,2006：12(10)：752-754,764.
[18]吴以岭.中医络病学说与三维立体网络系统.中医杂志,2003；44(6)：407-409.
[19]杨广,张敏州.邓铁涛教授治疗急性心肌梗死冠脉介入术后验案举隅.实用中医内科杂志,2005；19(5)：415.
[20]吴伟康,邓铁涛.邓老“痰瘀相关”理论与冠心病防治.深圳中西医结合 杂,2006：16(1)：13-16,20.
[21]邢丽,李鑫.辩证分型治疗冠心病心绞痛浅识.实用中医内科杂志,2007；21(5)：39.
[22]其其格,王伟,胡立,等.9790例冠心病心绞痛辨证分型文献统计分析.山西中医,2008：24(10)：31-33.
[23]郭志华.冠心病心绞痛2432例中医辨证分型综合统计分析.湖南中医杂志,1998：14(2)：7-8.
[24]吴辉,于扬文,吴伟,等.116例冠心病患者中医证候及病因分析.江苏中医药,2004；25(10)：30-31.
[25]郑筱萸主编.中药新药临床研究指导原则.北京,中国医药科技出版社.2002年版.
[26]王先敏,李鹏,阿娜尔汗.冠心病从痰瘀论治的客观基础与机制探析.实用中医内科杂志.2006；20(2)：124.
[27]方显明,黄红英.冠心病心绞痛从痰论治探讨.广西中医药,2001；24(1)：42-43.
[28]靳华.浅谈冠心病从痰瘀分型论治.光明中医,2009；24(9)：1787-1788.
[29]韩丽华,吴鸿,吕翠田,等.宽胸丹治疗痰瘀阻滞型胸痹(冠心病心绞痛)临床观察.河南中医.2005：25(1)：35-37.
[30]张效科,马松涛,杨磊,等.冠心病从肾论治的理论依据及意义.四川中医,2004：22(4)：18-19.
[31]张晓星,龚恬,张立平.冠心病从肾论治.新中医,2008；40(5)：3-4.
[32]鲁厚年.补肾化瘀法治疗冠心病心绞痛48例.中国现代医生,2009；47(2)：73-74.
[33]郑耀庭.浅谈从肝论治冠心病.中国中医基础医学杂志,2002；8(10)：40-41.
[34]周承志,唐娟.冠心病从肝论治五法.湖北中医杂志,2001；23(10)：19.
[35]胡贤琼.从肝论治冠心病心绞痛32例.四川中医,2004；22(1)：36-37
[36]苗阳,高铸烨.冠心病从风论治浅谈.庆祝中国中医研究院成立50周年首届中医药发展国际论坛暨首届中医药防治艾滋病国际研讨会论文,北京,2005：610-613.
[37]陈锋,王文文.再探冠心病从肺论治.现代中西医结合杂志,2002；11(6)：547.
[38]王霭平.从肺论治胸痹心痛的临床观察.上海针灸杂志,2004；23(4)：25.
[39]王香存.谈冠心病心绞痛从脾胃论治.河南中医学院学报,2005；20(3)： 44-45.
[40]李宁.从脾胃论治冠心病心绞痛72例.甘肃中医学院学报.2004,21(4)：32-33.
[41]戴瑞鸿.我与麝香保心丸.中国中西医结合杂志,2000；20(3)：243-244
[42]金椿,王受益,戴瑞鸿.麝香保心丸对16例冠心病心绞痛患者运动耐量的影响.上海医药,1997；18(5)：23-26.
[43]吕国庆,戴瑞鸿.顾家韵,等.麝香保心丸在不稳定性心绞痛治疗中的作用.中西医结合杂志,1987：7(7)：405-406.
[44]上海市麝香保心丸协作组.麝香保心丸治疗冠心病心绞痛的疗效观察.中成药研究.1984,6(3)：21-23.
[45]常以芳,韩瑞丰,韩海英,等.麝香保心丸与消心痛治疗冠心病的临床疗效观察.上海医药,1996：17(12)：12-13.
[46]沈玉芳,陈大年,王邦宁,等.麝香保心丸与消心痛患者冠心病心绞痛的对比性研究.上海医药,1996：17(12)：22-24.
[47]魏艳阳,周明银.麝香保心丸治疗冠心病不稳定型心绞痛临床观察.中国现代药物应用.2009,3(9)：14-15.
[48]王蕾,熊泽宇,王刚.复方丹参滴丸治疗稳定型心绞痛随机对照试验的系统评价[J].中国中西医结合杂志,2004；24(6)：500—504.
[49]张敏州,张俭.复方丹参滴丸治疗冠心病的Meta分析.时珍国医国药,2009；20(4)：1007—1008.
[50]陈焕清,熊小强,段朝晖,等.复方丹参滴丸对冠心病血管内皮功能的干预及其机制.中山大学学报(医学科学版),2009；30(4S)：221-223.
[51]殷建明,罗陆一,张大创,等.通心贴穴位外治冠心病心绞痛临床研究.中西医结合心脑血管病杂志,2009；7(10)：1138-1140.
[52]张明雪,常艳鹏,曹洪欣.温阳活血中药复方调控冠心病(心)阳虚血瘀证大鼠血小板内受体、信号转导的作用机制研究.中华中医药杂志.2008,23(6)：494-497.
[53]郑丽艳,张桂红,吴庆田,等.纳米中药心肌益生散对心肌细胞增殖的影响.黑龙江医药科学,2009；32(4)：18-19.
[54]张传清,施麟,黄建萍,等.安心颗粒治疗冠心病心绞痛实验研究.中国中医急症.2004,13(9)：613-614.
[55]Braunwald E, Mark DB, Jones RH, et al. Unstable angina:diagnosis and management. Rockvilles M D:Agency for Health Care Policy and Research and the National Heart, Lung, and Blood Institute, US Public Health Service, US Department of Health and Human Services:1994:1;Publication No 94-0602.
[56]王吉耀主编.内科学.北京：人民卫生出版社,2005年8月第一版.
[57]吴兆苏,姚崇华,赵冬,等.我国多省市心血管趋势决定因素的人群检测(中国MONICA方案)发病率和死亡率检测结果.中华心血管病杂志.1997；25(1)：6-11.
[58]Abdelmout I, DANCHIN N, ILARDO C, et al. C-reactive protein and coronary artery disease:Additional evidence of the implication of an inflammatory process in acute coronary syndromes. Am Heart J,1999,137(2): 346-351.
[59]Libby P, Ridker PM, Maseri A. Inflammation and atheroaclerosis. Circulation,2002,105:2092-2197.
[60]Hartford M, Wiklund 0, Mattsson-Hulen L, et al.C-reactive protein, interleukin-6, secretory phoSpholipase a group II A and intercdular adhesion moleculel in the prediction of late outcome events after acute Coronary syndromes. J Intern Med,2007,262(5):526-536.
[61]田学增.阿奇霉索干预急性冠脉综合征对其心脏不良事件再发生的影响.第二军医大学学报,2003；24(24)：772.
[62]曹建红.急性冠脉综合征与C一反应蛋白、尿酸、颈动脉内一中膜厚度的相关性分析.浙江临床医学,2009；11(4)：374-376.
[63]Pasterkamp G, Schoneveld AH, Hijnen DJ, et al. Atheroselemtic arterial remodeling and the localization of macrophages and matrix metalloproteases 1,2 and 9 in the human coronary artery [J]. Atherosclerosis, 2000,149(2):245-253.
[64]Lamberl E, Dasse E, Haye B。etal. TIMPs as multifacial proteins. Crit Rev Oncol Hematol,2004,149(3):187-198.
[65]Leu HB,Lin CP, Lin WT, etal.Circulating mononuelear superoxide production and inflammatory markers for long term prognosis in patients with cardiac syndrome X[J]. Free Radic Biol Med,2006; 40(6):983-91.
[66]Tai MH, Kuo SM, Liang liT, et aL Modulation of angiogenie processes in cultured endothelial cells by low density lipoproteim subfraetions from patients with familial hypercholesterolemia[J].Atherosclerosis,2006; 186(2): 448-57.
[67]赖泽仁,李凌,金焱.缺血修饰白蛋白在老年急性冠脉综合征诊断中的应用.中国老年学杂志,2007；27(13)：1267-1269.
[68]黄晓华,肖婷.急性冠脉综合征患者缺血修饰白蛋白的检测及临床应用.医学临床研究,2009；26(11)：2109-2111.
[69]Shmuel Schwartzenberg, Varda Deutsch, Sofia Maysel-Auslender, et al. Circulating Apoptotic Progenitor Cells:A Novel Biomarker in Patients With Acute Coronary Syndromes. Arterioscler Thromb Vasc Biol.2007,5:27-31.
[70]Brays Genis A, Conover CA, Overgaard MT, etal. Pregnancy associated plasma protein A as a marker of acute coronary syndromes[J]. N Engl J Med, 2001,345(14):1022-1029.
[71]Qin QP, Laitinen P, Majamaa-Voltti K, et al. Release patterns of pregnancy associated plasma protein A(PAPP-A)in patients with acute coronary syndromes [J]. Stand Cardiovasc J,2002,36(6):358-361.
[72]段樱,谭兵。刘树业.两种心脏标志物诊断急性冠脉综合征的对比研究.山东医药,2009,49(16)：90-91.
[73]刘荣静,习浩.急性冠脉综合征早期诊断中不同血清标记物组合的比较.循证医学,2009,9(5)：309-313.
[74]Kilcullen N, Viswanathan K, Das R, et al. Heart-type fatty acid binding protein predicts long term mortality after acute coronary syndrome and identifies high risk patients across the range of troponin values [J]. Journal of the American College of Cardiology.2007,50(21):2061-2067.
[75]Matsumura T, Saito T, Fujimura H, et al. Cardiac troponin 1 for accurate evaluation of cardiac Status in myopathic patients [J]. Brain and Development, 2007,29(8):496-501.
[76]陈晓园,彭鹏.心型脂肪酸结合蛋白对急性冠脉综合征的诊断价值.中国全科医学.2009,12(24)：2253-2254.
[77]Angiolillo DJ, Guzman LA. Clinical overview of promising nonthienopyridine antiplatelet agents[J], Am Heart J,2008,156(2 suppl): s23-s28.
[78]de Gaetano G, Donati MB, Cerietti C. Prevention of thrombosis and vascular infllammation:benefit and limitations of selective or combined COX-1. COX-2 and 5-LOX inhibitors[J]. Trends Phannacol Sci,2003,24(5): 245-252.
[79]Nicholas B Norgard, Mazen Abu-Fade. Comparison of prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Vascular Health and Risk Management 2009:5 873-882.
[80]MeCann CJ. Menown IB. New anticoagulant strategies in ST elevation myocardial infarction:trials and clinical implications [J]. Vasc Health Risk Mansg。2008,4(2):305-313.
[81]黄宏星.近期发布几项血栓抗凝药物临床应用中国专家共识介绍.中国医药 导刊.2009,11(10)：1638-1639.
[82]何川,燕纯伯.急性冠脉综合征抗凝治疗进展.心血管病学进展.2008,29(5)：764-767.
[83]杨新春.急性冠脉综合征抗凝与抗血小板治疗.医师进修杂志(内科版),2004：27(10)：6-9.
[84]Braunwald E et al. American College of ardiology (ACC)and the American Heart Association (AHA) Guidelines, USA:ACC/AHA; 2002.
[85]Koga H, Sugiyama S, Ogawa H. Acute coronary syndrome related factors[J]. Nippon Rinsho,2006; 64(4):642-6.
[86]Souza-Coata DC, Figueiredo-Lopes L, Alves-Fiiho JC, etal. Protective effects of atorvsstatin in rat models of acute pulmonary embolism:involvement of matrix metalloproteirmse-9 [J]. Crit Care Med.2007; 35(1):239-245.
[87]Libby P. Inflammation and Atherosclerosis[J]. Circulation,2002, 105(9):1135-1143.
[88]Olsson AG, Schwartz GG, Szarck M, et al. Effects of high-dose atorvastatin in patients>or=65 years of age with acute coronary syndrome (from the myocardial ischemia reduction with aggressive cholesterol lowering [MIRAC] study) [J]. Am J Cardiol.2007,99(5):632-635.
[89]刘甲兴,芮磊,洪原,等.急性冠脉综合征入院即刻应用辛伐他汀对炎症因子的影响.临床军医杂志.2009,37(4)：607-609.
[90]马风英,姚青海,吴尚勤,等.阿托伐他汀对急性冠脉综合征患者MMP9／TIMPl及预后的影响.天津医药.2009,37(8)：701-702
[91]艾德惠,蔡志友,陈和,等.急性冠脉综合征血清OX—LDL水平及阿托伐他汀的干预作用.中国老年学杂志.2009,29(15)：1958-1960.
[92]Nissen SE, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C reactive protein, and coronary artery disease N Engl J Med 2005; 352(1):29-38.
[93]Smith SC Jr., Feldman TE, Hirshfeld JW Jr, et al. ACC/AHA/SCAI 2005 guideline update for percutoneous coronary intervention a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol,2006,47:121.
[94]Antman EM, Hand M, Armstrong PW. et aL 2007 Focused Update of the ACC /AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction:A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol,2008, 51：210-247.
[95]周玉杰,杨士伟.急性冠脉综合征抗栓与溶栓治疗.临床药物治疗杂志,2009：7(3)：12-16.
[96]周延民,刘春,贺晓晶.急性冠脉综合征药物治疗进展.中国医学创新.2009,6(28)：186-187.
[97]高润霖.从急性心肌梗死治疗指南看再灌注治疗策略的选择.中华心血管病杂志,2005,33(11)1061-1064.
[98]From AM, Rihal CS, Lennon RJ, et al.Temporal trends and improved outcomes of percutaneous coronary revascularization in nonagenarians [J]. JACC Cardiovasc Inten,2008,1(6):692-698.
[98]Overbaugh KJ. Acute Coronary syndrome [J]. Am J Nurs,2009,109(5): 42-52.
[100]Chanwalit N, Yipintsoi T, Treankosol D, et al. Prognostic value of Selected presenting features of acute coronary syndrome in predicting inhospital adverse events:insight from the acute coronary syndrome registry[J]. Intern Med,2009,48(9):639-646.
[101]中华医学会心血管学分会.不稳定性心绞痛诊断和治疗建议[J].中华心血管病杂志,2000：28(6)：409—412.
[102]中华医学会心血管学分会.急性心肌梗死诊断和治疗指南[J].中华心血管病杂志,2001,29(12)：710—725.
[103]Antman et al.. ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction.2004 ACC/AHA Practice Guidelines.1-211.
[104]The task force on the management of ST- segment elevation acute Myocardial Infarction of the European Society of Cardiology. Management of acute Myocardial Infarction in patients presenting with persistent ST- segment elevation. European Heart Journal.2008(29):2909-2945.
[105]沈绍功,王承德,闫希军.中医心病诊断疗效标准与用药规范.北京,北京出版社,2002年2月第1版.
[106]吴伟康,候灿,罗汉川,等.垂体后叶素性心肌缺血模型再探[J].中国病理生理杂志.1993.9(2)：124.
[107]徐叔云.药理学实验方法第2版.北京：人民卫生出版社.1991,897.
[108]胡东裴,胸痹证治文献研究.山东中医药大学学报,2005；29(1)：37-40.
[109]方青,詹小萍,莫剑翎,等.黄连解毒汤对AD大鼠的治疗作用及对细胞因子含量的影响.中国中药杂志,2004；29(6)：575-578.
[110]Conti CR. Update pathophysiologic concepts in unstable coronary artery disease. Am Heart J,2001,141:S12.
[111]侯家玉.中药药理学.北京：中国中医药出版社,2002,39-66,202-242.
[112]王本祥.现代中药药理学.天津：天津科学技术出版社,1997：915,368.
[113]张京春,陈可冀,张文高,等.不稳定斑块的中西医结合认识现状及研究思路.中国中西医结合杂志,2005；25(10)：869-871.
[114]Wen C, Xu H, Huang QF, et al. Effect of drugs for promoting blood circulation on blood lipids and inflammatory reaction of atherosclerotic plaques in apoE gene deficiency mice. Chi J Integr Tradit West Med 2005: 25(4):345-349.
[115]吴辉,洪永敦,吴伟,等.冠心病痰热证候与炎症因子相关性探讨.辽宁中医杂志,2004；31(7)：52-543.
[116]黄衍寿,莫鸿辉,洪永敦,等.清热解毒法治疗急性冠脉综合征55例.广州中医药大学学报,2006；23(1)：13-16.
[117]陈可冀,史载祥.凋亡因子在冠心病中的作用及活血化瘀药对其干预的影响.中国中医基础医学杂志,2008；14(4)：280-282.
[118]李敏王硕仁赵明镜,等.活血益气方药对心肌梗死后心力衰竭大鼠心肌细胞凋亡的影响.中西医结合心脑血管杂志,2005；3(1)：33-35.
[119]常志文,刘琦.缺血再灌注心肌细胞凋亡及药物干预.中国新药杂志,2000；9(1)：28.
[120]李源段红王天成,等.川芎嗪对再灌注大鼠心肌细胞c-fos基因表达凋亡的影响.心脏杂志.2000,12(3)：213.
[121]赵明中,刘岚,汪家瑞,等.通心络胶囊对异丙肾上腺素致鼠心肌损伤保护作用的实验研究.中国中西医结合杂志,2001；21(1)：51.
[122]李锦山,李国辉,缪英年,等.川芎嗪抗大鼠心肌缺血及抗心细胞凋亡作用.中国实用医药,2008；3(32)：1-2.
[123]陈俊荣,陈俊红,王梅,等.酒大黄对动脉粥样硬化兔血脂水平的影响.中国医药导刊.2009：11(11)：1899-1900.
[124]朱郁文.浅析大黄的几种炮制方法及其影响.中医药导报,2007；13(8)：91-92
[125]侯改霞,杨建雄.连翘叶茶提取物对力竭运动及恢复期小鼠心肌抗氧化酶和LDH同工酶活性的影响.中国运动医学杂志.2006,25(1)：90-92
[126]梁日欣,廖福龙,韩东.川芎嗪预处理对麻醉家兔心肌缺血再灌注损伤的保护作用.中药药理与临床,2000,16(2)：11
[127]Kato T, Noguchi K, Sakanashi M, et al. Effects ofthe water extract of Chrysanthemum indicum Linn on coronary and systemic hemodynamics in the dog[J]Arch hat Phacmacodyn Ther,1986,280(2):241-253.
[128]陈铎葆,张雷,孙静文,等.红花水提物对心肌缺血大鼠的血液流变学与血小板聚集影响的实验研究.中国中医药科技,2004.11(5)：290.
[129]王艳春,张忠艳,姜小卓.中药黄芩的药理及应用.中外医疗.2009,28(13)：158
[130]莫晓燕,黄海霞,洪喻,等.赤芍总苷对培养乳鼠心肌细胞损伤的抗氧化作用.中国药理学通报,2004,20(10)：1119—1121.
[131]许春华,刘秀芝.急性冠脉综合征中医症型分布规律及临床观察.中外健康文摘,2009；8(12)：10-12.
[132]魏丹霞,刘明,庞永诚,等.111例冠心病患者中医证型分布规律研究.云南中医中药杂志,2008；29(7)：7-8.
[133]陈力,肖政.急性冠脉综合征中医证候回顾研究.广州中医药大学学报,2008；25(3)：248-250.
[134]李延芳.血府逐瘀汤治疗气滞血瘀型心绞痛30例.现代中医药,2008；28(2)：17-18.
[135]郑春松,黄钦,李旭东,等.血府逐瘀汤在心血管疾病方面的计算机药理学探讨.计算机与应用化学,2009；26(1)：9-16.
[136]王少英.清热解毒药物在治疗冠心病中的运用.北京中医杂志,2004；23(1)：14—15.
[137]钱卫东,陈晓虎.清热活血法干预急性冠脉综合征炎症反应的临床观察.湖北中医杂志,2010；32(1)：17-18.
[138]李娟,罗小星.建立中医危重病评分系统的初步探讨.中国中医急症,2009；18(6)：925-926。
[139]俞建华,刘新兵,方旭成,等.入院时APACHE—Ⅱ评分在急性心肌梗死患者危险分层中的应用价值.实用诊断与治疗杂志,2008；22(3)：163-164.
[140]汤日波,刘晓辉,谢莲娜,等.APACHEⅡ评分在急性冠脉综合征中的应用.中华急诊医学杂志,2005；14(8)：682-683.
[141]梅运清,季强,冯靖,等.冠状动脉旁路移植术后全身炎性反应综合征患者APACHEIII评分与炎症介质的相关性研究.中华医学杂志,2006；86(13)：927-929.
[142]顾伟,殷文朋,李春盛.肌钙蛋白Ⅰ和APACHE-Ⅱ评分在危重病患者预后中的应用价值[J].中国实用内科杂志,2007；27(17)：1373-1375.
[143]Knaus W A, Zinmerman J E。Wagner D P, et al. APACHEII:a severity of disease classification system[J]. Cirt Care Med,1983,13(10):818-826.
[144]speidl W S, Graf s, Hornykewycz S, et al. High sensitivity C-reactive protein in the prediction of coronary events in patients with premature coronary artery disease[J]. Am Heart J,2002,144(3):449.
[145]Yoshiya Monden, Toru Kubota, Takaki Tsutsumi, et al. Soluble TNF receptors prevent opoptosis in infiltrating cells and promote ventricular rupture and remodeling after myocardial infarction[J]. Cardiovascular Research,2007, 73(4):794-805.
[146]Mach F, Schonbeck U, bbby P. CD40 signaling in vascular cells:akeyrole in atherosclerosis. Atherosclerosis,1998,137(suppl):S89-S95.
[147]付瑜,姜树民.建立急性冠状动脉综合征动物模型的研究.中华中医药学刊,2007：25(1)：105-107.
[148]施新献.现代医学实用动物学.北京：人民军医出版社.2000：442—444.
[149]王洁,吕吉元,张明升,等.清醒无拘束大鼠心肌缺血模型的制备.山西医科大学学报,2007；38(5)：398-400.
[150]吴伟康,周琳,孙慧兰.四逆汤对心肌缺血大鼠心肌内皮素影响的实验研究.中国中西医结合杂志,2002；22(8)：610-612.
[151]吴伟康,侯灿,罗汉川,等.垂体后叶素性心肌缺血模型再探.中国病理生理杂志,1993：9(2)124-127.