葱白提取物防治冠心病心肌缺血临床和实验研究
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摘要
目的:
     1、通过观察葱白提取物对冠心病心肌缺血患者的临床症状、体征、心电图、血液流变学、血脂等指标的影响,研究葱白提取物治疗冠心病心肌缺血的疗效及机制。
     2、通过观察葱白提取物对猪缺血心肌能量代谢及微循环的影响,探讨其对心肌的保护作用及机制。
     3、通过临床与实验研究,初步从一个侧面阐明“阳气不通”和冠心病发病的关系,为通阳法防治冠心病提供理论依据。
     方法:
     第一部分临床研究:选择2005年7月~2007年8月武汉市第一医院、湖北省中医院门诊及心内科病房冠心病心肌缺血患者100例,根据中医诊断标准进行证型分类,并随机分为治疗组和对照组各50例。用药前两组病人停用一切中药和硝酸酯类药物5天,观察中两组常规治疗不变,劳力维持原状不变,治疗期间嘱患者低盐低脂饮食,适量运动。对照组药物选用速效救心丸治疗,每次10粒,每日2次。葱白提取物由武汉市中西医结合医院药剂科提供,每次2粒,每日2次,四周为一个疗程,停药2周后观察疗效。观察药物的安全性、治疗前后临床症状和体征评分、心电图改变、血液流变学及血脂等指标。
     第二部分实验研究:将24只猪随机分为空白模型组,假手术组,葱白提取物组,曲美他嗪组4组,每组6只。通过球囊封堵冠状动脉前降支60min制备猪心肌缺血模型,术后第四天予以等体积的生理盐水、葱白提取物,曲美他嗪治疗28天,然后行~(13)N-NH3、~(18)F-FDG PET/cT心肌显像检测。对左心室心肌断层图像进行分析,明确通阳中药葱白提取物对心肌能量代谢和微循环的影响以及二者之间的相关性。
     结果:
     第一部分临床研究:临床观察研究结果,两个治疗组患者的年龄、性别和病程均无显著性差异(P>0.05),两组病例对冠心病症状的改善均有一定作用,葱白提取物治疗组总有效率93.75%,速效救心丸组对照组总有效率91.67%(P>0.05},治疗后心电图改善总有效率无明显的差异(P>0.05);葱白提取物组治疗后血小板最大聚集率、全血粘度、血浆粘度、红细胞压积、纤维蛋白原、CRP明显下降与救心丸组治疗后比较无显著性差异(P>0.05),血脂水平LDL明显下降,HDL明显上升,与救心丸组治疗后比较显有著性差异(P<0.05)。
     第二部分实验研究:空白模型组,在54个心肌节段中,有心肌活力的节段为28个(51.85%);假手术组,~(13)N-NH_3 PET心肌灌注显像与~(18)F-FDGPET心肌代谢显像一致,54个心肌节段均示正常;葱白提取物组,在54个心肌节段中,有心肌活力的节段为44个(81.48%);曲美他嗪组,在54个心肌节段中,有心肌活力的节段为41个(75.93%)。葱白提取物组、曲美他嗪组与空白模型组有活力的心肌节段数有显著性差异(P<0.01);葱白提取物组与曲美他嗪组有活力的心肌节段数无显著差异性(P>0.05)。
     结论:
     1、葱白提取物治疗冠心病心肌缺血安全有效:葱白提取物临床应用于治疗冠心病安全性大、疗效肯定、副作用小。在临床疗效评价上,虽然两组总有效率无显著差异,但是葱白提取物能够较大程度的缓解冠心病患者的心绞痛症状(包括心绞痛发作的次数、持续的时间、疼痛的程度),改善心电图的心肌缺血表现。
     2、葱白提取物通过调节脂质代谢,防治冠心病:动脉粥样硬化是冠心病发生发展的病理基础,而脂质代谢异常是导致动脉粥样硬化的重要原因,调节脂质代谢异常是防治冠心病的有效手段,葱白提取物能够明显的降低血脂水平,进而抗动脉粥样硬化、延缓冠心病的进程。
     3、葱白提取物可以促进缺血心肌微循环改善心肌缺血:葱白提取物能够明显的降低血小板最大聚集率、全血粘度、血浆粘度、红细胞压积、纤维蛋白原,同时可以明显改善缺血心肌的血流灌注,促进血液循环改善心肌缺血。
     4、葱白提取物可以优化能量代谢,抗氧化损伤,保护心肌细胞:缺血心肌由于缺血缺氧而导致细胞能量代谢异常,产生大量的氧自由基损伤心肌细胞,研究表明葱白提取物可以优化心肌细胞能量代谢,保护猪缺血心肌。
     5、“阳气不通”是导致心肌缺血的重要原因,“通阳法”是治疗心肌缺血的重要手段,值得深入研究:临床和实验研究均表明:用通阳中药治疗心肌缺血安全有效,对各型冠心病心肌缺血患者均有较好的疗效,说明心肌缺血的发生与“阳气不通”密切相关,阳气不通既可能是导致心肌缺血的始动因素,也可能是其它原因导致心肌缺血后的主要临床表现。和曲美他嗪不影响血流动力学不同,葱白提取物不仅可以影响血流动力学,而且可以改善心肌能量代谢,体现了中医药多系统、多靶点的疗效优势。因此,及时有效的“通阳”治疗是改善心肌缺血的有效途径,值得深入研究。
Object:
     1、To observe the effect of clinical symptoms、signs、electrocardiogram、blood rheology、blood lipids and other indicators by Allium Stalk extract of myocardial ischemia in coronary heart disease Patients,Research on Allium Stalk extract treatment of coronary heart disease the effect of myocardial ischemia and its mechanism.
     2、To observe the effect of Energy metabolism and microcirculation to swines of myocardial ischemia,To investigate its role in myocardial protection and mechanism.
     3、By Research of clinical and experiment,from one side to clarify the initial "barrier yang" and the relationship between coronary heart disease,Yang method for providing a theoretical basis for prevention and treatment of coronary heart disease.
     Method:
     The first part of clinical research:Select July 2005-August 2007 First Hospital of Wuhan City,Hubei Province,Chinese medicine hospital out-patient clinics and medical wards of the heart in patients with coronary heart disease 100 cases of myocardial ischemia,according to TCM diagnostic criteria for evidence-based classification,and random divided into treatment group and 50 cases of the control group.Two groups of patients before treatment and nitrate medicine out all five days of drugs observed in conventional treatment of the two groups remains unchanged,the labor to maintain the status quo remains unchanged,during treatment ask Patientslow-fat low-salt diet,regular exercise. Jiuxin pill drug selection of the control group treatment,each 10, 2 times daily,Allium Stalk extract from Wuhan City in the provision of Integrated Traditional and Western Medicine Hospital Pharmacy, 2 each,2 times daily,for a four-week course of treatment, observation of drug effect after 2 weeks.Observe the safety,the treatment of clinical symptoms and signs before and after the score, ECG changes,hemorheology and blood lipid were measured.
     The second part of experimental research:The 24 pigs were randomly divided into blank model group,sham-operated group,Allium Stalk extract group trimetazidine group 4 groups 6.Through the balloon occluder 60min anterior descending coronary artery preparation of porcine myocardial ischemiamodel,such as after the fourth day to be the volume of normal saline,Allium Stalk extract,trimetazidine treatment of 28 days,and then line ~(13)N-NH_3,~(18)F-FDG PET/CT detection of myocardial perfusion imaging.Of left ventricular myocardial SPECT image analysis of Allium Stalk extract on myocardial energy metabolism and microcirculation,as well as the correlation between the two.
     Results:
     The first part of clinical research:clinical observation study, the two treatment groups in patients with age,sex and disease were not significantly different(P>0.05),two groups of cases to improve symptoms of coronary heart disease have a certain role in the treatment of Allium Stalk extract The total effective rate 93.75%,control group Jiuxin pill group the total effective rate 91.67%(P>0.05);after treatment to improve the overall efficiency ECG no significant differences(P>0.05);stallion group treated extract maximum platelet aggregation the rate of whole blood viscosity,plasma viscosity,hematocrit,fibrinogen,CRP decreased Jiuxin pill group and after treatment showed no significant difference(P>0.05),decreased LDL lipid levels,HDL significantly increased,and Jiuxin pill comparison group after treatment had significantly difference(P<0.05).
     The second part of experimental research:gaps in the model group, in 54 myocardial segments,there are segments of myocardial viability for the 28(51.85%);sham-operated group,~(13)N-NH_3 PET myocardial perfusion imaging with ~(18)F-FDG PET myocardial metabolic imaging of the same 54 myocardial segments that were normal; stallion extract group,in 54 myocardial segments,there are segments of myocardial viability for the 44(81.48%);trimetazidine group,54 myocardial segments,there are segments of myocardial viability for the 41(75.93%).Allium Stalk extract group trimetazidine group and the blank model group dynamic number of myocardial segments were significantly different(P<0.01); stallion extract group and trimetazidine group dynamic myocardial segments no significant difference between the number of(P>0.05).
     Conclusion:
     1、Allium Stalk extract treatment of myocardial ischemia in coronary heart disease is safe and effective:Allium Stalk extract used in the treatment of coronary heart disease clinical safety,and efficacy of certain side effects.In the evaluation of clinical efficacy,although the efficiency of the two groups there was no significant difference,but Allium Stalk extract a higher degree of ease the symptoms of angina pectoris in patients with coronary heart disease(including angina attack frequency,duration,degree of pain and ease the way),to improve the performance of EGG of myocardial ischemia.
     2、Allium Stalk extract by regulating lipid metabolism,prevention and treatment of coronary heart disease:the pulse coronary atherosclerosis is the pathological basis of the occurrence and development,and abnormal lipid metabolism is atherosclerosis of vein important reason for regulation of lipid metabolism is abnormal coronary heart disease prevention effective means to extract stallion can significantly lower blood lipid levels,and anti-atherosclerosis,delaying the process of coronary heart disease.
     3、Allium Stalk extract can promote myocardial ischemia myocardial ischemia to improve microcirculation:very light blue extract can significantly reduce the maximum platelet aggregation rate,whole blood viscosity,plasma viscosity,hematocrit,fibrinogen,as well as significant improvement in ischemic myocardial blood flow, promote blood circulation to improve myocardial ischemia.
     4、Allium Stalk extract can optimize energy metabolism, anti-oxidative damage,the protection of myocardial cells: ischemic myocardium due to ischemia and hypoxia caused by abnormal cell energymetabolism,resulting in a large number of oxygen free radical injury of myocardial cells,the study shows that Allium Stalk extract can optimize myocardial cells energy metabolism, protection of porcine myocardial ischemia.
     5、"Yang barrier" is an important cause of myocardial ischemia, "Tung-yang," the treatment of myocardial ischemia is an important tool,it is worth in-depth study:clinical and experimental studies have shown that:The Yang of Chinese medicine is safe and effective treatment of myocardial ischemia,various types of myocardial ischemia in patients with coronary heart disease have a better effect on the occurrence of myocardial ischemia and "yang barrier" is closely related to both yang barrier may lead to myocardial ischemia is the initiating factor,or it may be other after myocardial ischemia causes the major clinical manifestations.And trimetazidine does not affect hemodynamics different stallion extracts can affect not only hemodynamics,but also improve myocardial energy metabolism,reflects the traditional Chinese medicine,multi-system,the efficacy advantage of multi-targets. Therefore,the timely and effective "yang" is to improve the treatment of myocardial ischemia in an effective way,it is worth in-depth study.
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