参术冠心颗粒抗心肌缺血的实验研究和临床研究
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摘要
研究目的
1实验部分：通过研究参术冠心方对大鼠心肌梗死模型心功能储备及冠脉微循环作用,探讨其抗心肌缺血作用的机理、验证其疗效。
2临床部分：冠心病稳定型心绞痛患者接受参术冠心方治疗后的疗效评价。评估参术冠心方对冠心病稳定型心绞痛患者心绞痛缓解程度、运动耐量、中医症候改善情况、生活质量的影响。
研究方法
1实验部分：健康SPF级SD大鼠60只,随机分成正常对照组(简称假手术组)、模型对照组(简称模型组)、参术冠心方高剂量组(简称高剂量组)、参术冠心病方中剂量组(简称中剂量组)、参术冠心方方低剂量组(简称低剂量组)、复方丹参滴丸对照组(简称丹参滴丸组),共6组,每组10只。后5组行结扎冠状动脉建立AMI大鼠模型,假手术组只穿线不进行结扎。造模3天后开始干预4周,测定4周后各组大鼠的血流动力学、心输出量、心肌标志物、梗死面积、梗死区中小血管MVC值、梗死边缘区PECAM-1(CD31)和VEGF免疫组化表达。
2临床部分：采用随机双盲对照的方法,纳入2010年1月至2011年6月在广州中医药大学第二附属医院(广东省中医院)心脏中心门诊及病房(包括总院,二沙岛,芳村,珠海及大学城分院)收治确诊为冠心病稳定型心绞痛的患者120例,分为试验组和对照组。两组接受规范的西医标准治疗基础上,试验组患者给予参术冠心方中药复方颗粒剂(由江阴制药厂制作),每日1包(12g/包),对照组患者给予安慰剂颗粒剂(由江阴制药厂制作),每日1包(12g/包)。干预时间3个月。观察治疗前后及治疗过程中心绞痛发作情况、中医症候计分、西雅图心绞痛生存质量量表等。
结果
1实验部分：参术冠心方高、中剂量组MAP、LVSP、 dp/dt max、 dp/dt min、Cardiac output与模型组对比,差异有统计学意义(P<0.05),呈剂量相关表现,与丹参滴丸组相比,差异有统计学意义(P<0.05),参术冠心方组优于模型组、丹参滴丸组。参术冠心方高剂量组心梗面积MI减少,与模型组差异有统计学意义(P<0.05),其余各组与模型组差异无统计学意义(P>0.05)。梗死区的心肌中小血管的MVC,梗死边缘区CD31及VEGF的表达,参术各剂量组与模型组相比表达明显增加差异有统计学意义(P<0.05),呈剂量相关表现,参术冠心方高剂量组与丹参滴丸组相比MVC、CD31、VEGF表达差异有统计学意义(P<0.05)。
2临床部分：治疗后两组绞痛发作次数、程度、持续时间、硝酸甘油总用量、长效硝酸脂类药物使用比率,胃粘膜保护剂使用比率、中医症候计分、西雅图心绞痛生存质量量表各维度计分比较,差异有统计学意义(P<0.05),试验组优于对照组。
结论
1参术冠心方能明显改善心肌梗死大鼠模型心功能储备及冠脉微循环状态,起到抗心肌缺血,保护心肌的作用。
2参术冠心方能改善冠心病稳定型心绞痛患者的心绞痛症状、改善心功能、提高患者日常活动耐量、保护胃肠功能、提高生活质量、改善中医症候,对血压心率无明显影响,依从性高,无明显毒副作用及不良反应。
Objecti ve
1Laboratory research:The aim of this study were studying the mechanism of anti-ischemic effects of shenshuguanxin prescription by studying its impact to cardiac function reserves and coronary microcirculation of the Experimental rat model of myocardial infarction.
2Clinical research:Clinical evaluation of patients with stable angina pectoris receiving prescription treatment. Assess the impact of prescription on patients with stable angina pectoris, including the degree of angina relief, exercise tolerance, TCM clinical symptoms improvement and quality of life.
Methods
1Laboratory research:A total of60healthy SPF SD rats were randomly divided into six groups (n=10), normal control group (sham operation group), model control group (model group), the prescription of high dose group (high dose group), the prescription of medium-dose group (middle dose group), prescription low dose group (low dose group), compound Danshen Dripping Pills in the control group (Danshen Dripping Pill group), respectively. The AMI rat model of myocardial infarction underwent coronary artery ligation, comparing with the sham operation group with needle pass through without ligation. The interventions were began at3days after modeling and lasted for4weeks. Measured data of rats in each group, including hemodynamics, cardiac output, cardiac markers, infarct size, small and medium-sized blood vessels MVC value of infarct zone, infarct border zone of PECAM-1and VEGF immune group of expression.
2Clinical research:The study used the method of double-blind, randomized, controlled. A total of120patients were involved and divided into treated group and control group, who were treated and diagnosed with stable angina pectoris from January2010to June2011, in clinics and wards of the Heart Center of the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (guangdong provcial hospital of TCM)(including the Hospital's headquarters, the Hospital's branch in Er Sha Island, Fangcun, Zhuhai and the University City). Two groups both accepted the norms of Western standard treatment, the treated group were treated with the prescription (produced by the Jiangyin Pharmaceutical Factory),1packet a day, the control group were treated with placebo formula (produced by the Jiangyin Pharmaceutical Factory),1packet a day, respectively. The intervention time was three months. Observed situations of these patient before, during and after treatment, including Angina pectoris attack, Chinese medicine symptom scoring, Seattle angina Quality of Life Scale.
Results
1Laboratory research:On comparison of MAP, UVSP, dp/dt max, dp/dt min and Cardiac output in high dose group and medium dose group of shenshuguanxin prescription and model group, there is statistical significant difference(P<0.05). And there is dose related expression. The shenzhuguanxin prescription group is better than model group and Danshen Dripping Pill group(P<0.05). There is decrease of infarct border zone MI in high dose group of shenzhuguanxin prescription group, and there is significant difference between high dose group of shenzhuguanxin prescription group and model group(P<0.05), and there are no significant differences between model group and the left of the groups(P>0.05). The increased expressions of MVC value of blood vessels in infarct zone, CD31of infarct border zone, and expression of VEGF is more than model group with significant difference(P<0.05) and dose relation. There is significant difference on comparison of MV^CD31> VEGF between shenzhuguanxin prescription group and Danshen Dripping Pill group (P<0.05).
2Clinical research:on comparison of rate, level, persistence time, total dose of Nitroglycerin, percentage use of long action Mononitrate ester healer, percentage use of gastric mucosa protecting drug, Chinese medicine symptom scoring, and Seattle angina Quality of Uife Scale, the treated group is better than control group with significant differences(P<0.05).
Conclusion:
1. Shenzhuguanxin prescription has reliable curative effects on improving the reservation of hear function, micro-recirculation state of coronary artery, anti myocardial ischemia, and protecting cardiac muscle of MI rat model.
2. Shenzhuguanxin prescription can decrease the symptoms of angina pectoris, improve the heart function, increase the toleration of patients' daily activities, protect the stomach intestine functions, improve the quality of life, and decrease the symptoms of Chinese medicine, with no infection of blood pressure and heat rate. It also has better compliance of patients, and no side effects.
1实验部分：通过研究参术冠心方对大鼠心肌梗死模型心功能储备及冠脉微循环作用,探讨其抗心肌缺血作用的机理、验证其疗效。
2临床部分：冠心病稳定型心绞痛患者接受参术冠心方治疗后的疗效评价。评估参术冠心方对冠心病稳定型心绞痛患者心绞痛缓解程度、运动耐量、中医症候改善情况、生活质量的影响。
研究方法
1实验部分：健康SPF级SD大鼠60只,随机分成正常对照组(简称假手术组)、模型对照组(简称模型组)、参术冠心方高剂量组(简称高剂量组)、参术冠心病方中剂量组(简称中剂量组)、参术冠心方方低剂量组(简称低剂量组)、复方丹参滴丸对照组(简称丹参滴丸组),共6组,每组10只。后5组行结扎冠状动脉建立AMI大鼠模型,假手术组只穿线不进行结扎。造模3天后开始干预4周,测定4周后各组大鼠的血流动力学、心输出量、心肌标志物、梗死面积、梗死区中小血管MVC值、梗死边缘区PECAM-1(CD31)和VEGF免疫组化表达。
2临床部分：采用随机双盲对照的方法,纳入2010年1月至2011年6月在广州中医药大学第二附属医院(广东省中医院)心脏中心门诊及病房(包括总院,二沙岛,芳村,珠海及大学城分院)收治确诊为冠心病稳定型心绞痛的患者120例,分为试验组和对照组。两组接受规范的西医标准治疗基础上,试验组患者给予参术冠心方中药复方颗粒剂(由江阴制药厂制作),每日1包(12g/包),对照组患者给予安慰剂颗粒剂(由江阴制药厂制作),每日1包(12g/包)。干预时间3个月。观察治疗前后及治疗过程中心绞痛发作情况、中医症候计分、西雅图心绞痛生存质量量表等。
结果
1实验部分：参术冠心方高、中剂量组MAP、LVSP、 dp/dt max、 dp/dt min、Cardiac output与模型组对比,差异有统计学意义(P<0.05),呈剂量相关表现,与丹参滴丸组相比,差异有统计学意义(P<0.05),参术冠心方组优于模型组、丹参滴丸组。参术冠心方高剂量组心梗面积MI减少,与模型组差异有统计学意义(P<0.05),其余各组与模型组差异无统计学意义(P>0.05)。梗死区的心肌中小血管的MVC,梗死边缘区CD31及VEGF的表达,参术各剂量组与模型组相比表达明显增加差异有统计学意义(P<0.05),呈剂量相关表现,参术冠心方高剂量组与丹参滴丸组相比MVC、CD31、VEGF表达差异有统计学意义(P<0.05)。
2临床部分：治疗后两组绞痛发作次数、程度、持续时间、硝酸甘油总用量、长效硝酸脂类药物使用比率,胃粘膜保护剂使用比率、中医症候计分、西雅图心绞痛生存质量量表各维度计分比较,差异有统计学意义(P<0.05),试验组优于对照组。
结论
1参术冠心方能明显改善心肌梗死大鼠模型心功能储备及冠脉微循环状态,起到抗心肌缺血,保护心肌的作用。
2参术冠心方能改善冠心病稳定型心绞痛患者的心绞痛症状、改善心功能、提高患者日常活动耐量、保护胃肠功能、提高生活质量、改善中医症候,对血压心率无明显影响,依从性高,无明显毒副作用及不良反应。
Objecti ve
1Laboratory research:The aim of this study were studying the mechanism of anti-ischemic effects of shenshuguanxin prescription by studying its impact to cardiac function reserves and coronary microcirculation of the Experimental rat model of myocardial infarction.
2Clinical research:Clinical evaluation of patients with stable angina pectoris receiving prescription treatment. Assess the impact of prescription on patients with stable angina pectoris, including the degree of angina relief, exercise tolerance, TCM clinical symptoms improvement and quality of life.
Methods
1Laboratory research:A total of60healthy SPF SD rats were randomly divided into six groups (n=10), normal control group (sham operation group), model control group (model group), the prescription of high dose group (high dose group), the prescription of medium-dose group (middle dose group), prescription low dose group (low dose group), compound Danshen Dripping Pills in the control group (Danshen Dripping Pill group), respectively. The AMI rat model of myocardial infarction underwent coronary artery ligation, comparing with the sham operation group with needle pass through without ligation. The interventions were began at3days after modeling and lasted for4weeks. Measured data of rats in each group, including hemodynamics, cardiac output, cardiac markers, infarct size, small and medium-sized blood vessels MVC value of infarct zone, infarct border zone of PECAM-1and VEGF immune group of expression.
2Clinical research:The study used the method of double-blind, randomized, controlled. A total of120patients were involved and divided into treated group and control group, who were treated and diagnosed with stable angina pectoris from January2010to June2011, in clinics and wards of the Heart Center of the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (guangdong provcial hospital of TCM)(including the Hospital's headquarters, the Hospital's branch in Er Sha Island, Fangcun, Zhuhai and the University City). Two groups both accepted the norms of Western standard treatment, the treated group were treated with the prescription (produced by the Jiangyin Pharmaceutical Factory),1packet a day, the control group were treated with placebo formula (produced by the Jiangyin Pharmaceutical Factory),1packet a day, respectively. The intervention time was three months. Observed situations of these patient before, during and after treatment, including Angina pectoris attack, Chinese medicine symptom scoring, Seattle angina Quality of Life Scale.
Results
1Laboratory research:On comparison of MAP, UVSP, dp/dt max, dp/dt min and Cardiac output in high dose group and medium dose group of shenshuguanxin prescription and model group, there is statistical significant difference(P<0.05). And there is dose related expression. The shenzhuguanxin prescription group is better than model group and Danshen Dripping Pill group(P<0.05). There is decrease of infarct border zone MI in high dose group of shenzhuguanxin prescription group, and there is significant difference between high dose group of shenzhuguanxin prescription group and model group(P<0.05), and there are no significant differences between model group and the left of the groups(P>0.05). The increased expressions of MVC value of blood vessels in infarct zone, CD31of infarct border zone, and expression of VEGF is more than model group with significant difference(P<0.05) and dose relation. There is significant difference on comparison of MV^CD31> VEGF between shenzhuguanxin prescription group and Danshen Dripping Pill group (P<0.05).
2Clinical research:on comparison of rate, level, persistence time, total dose of Nitroglycerin, percentage use of long action Mononitrate ester healer, percentage use of gastric mucosa protecting drug, Chinese medicine symptom scoring, and Seattle angina Quality of Uife Scale, the treated group is better than control group with significant differences(P<0.05).
Conclusion:
1. Shenzhuguanxin prescription has reliable curative effects on improving the reservation of hear function, micro-recirculation state of coronary artery, anti myocardial ischemia, and protecting cardiac muscle of MI rat model.
2. Shenzhuguanxin prescription can decrease the symptoms of angina pectoris, improve the heart function, increase the toleration of patients' daily activities, protect the stomach intestine functions, improve the quality of life, and decrease the symptoms of Chinese medicine, with no infection of blood pressure and heat rate. It also has better compliance of patients, and no side effects.
引文
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