十枣汤合葶苈子方治疗心力衰竭的临床与实验研究

【作者】 王萧；

【导师】 陈镜合；

【作者基本信息】 广州中医药大学 ， 中医内科学， 2000， 博士

【摘要】 一、概述 充血性心力衰竭（CHF）属内科常见重症，各种内外因素导致心脏长时间负荷过重、心肌病损及收缩力减弱，都可导致CHF，其临床死亡率较高。有器质性心脏病，年龄大，且有严重心功能障碍者5年存活率＜50％。目前，由于我国人民生活水平的提高，饮食结构的改变，临床上CHF的发病率亦日益增多。 西医药对CHF的治疗原则包括减轻心脏负荷、增强心脏收缩能力等，其中强心药和利尿剂的使用是常规的治疗方法。但这两类药的使用也存在一些问题，比如利尿剂持续大量使用可导致严重的电解质和酸碱平衡失调，强心药中洋地黄的治疗量与中毒量较为接近，且个体差异较大，易受体液环境波动的影响。 心力衰竭属中医学心悸、水肿、喘证、心痹、痰饮等范畴。祖国医学认为心衰的产生，多因心病日久迁延，又感受外邪、情志失调、劳倦过度或妊娠分娩等而诱发。近十多年来，中医药在治疗本病方面进行了大量的临床及实验研究，内容涉及多个方面。这些文献认为中药制剂无明显肝肾功能损害及不良反应，有的与西药组比较差异显著，但这些研究多以益气温阳为治疗原则，所选中药功效亦偏于温补，临床起效慢，疗程长。有些临床设计方法不科学，有的报道仅限于案例总结，并且设立自身对照观察和西药对照组者少，这些因素都影响了临床疗效的评价。 十枣汤为伤寒名方，在仲景原文中主治有形之水客居胸胁、引胁下痛的悬饮证。现代医家经过多方验证，将其治疗范围扩大为治疗各种水饮停聚胸腹属邪实之证，如肝硬化腹水、胸水、肾性水肿等，均可应用，但文献检索未见有该方治疗CHF的报道。葶苈子味辛苦，性寒，功可泻肺定喘、行水消肿。药理学研究证明葶苈子的有效成分葶苈子醇具有多种强心甙成分，能使心肌收缩力增强，心率下降，对衰弱心脏可增加输出量，其抗心衰机理与洋地黄类似。但葶苈子的有效成分含量较低，需较大剂量使用方能发挥作用。 十枣汤加葶苈子方是著名中西医结合专家陈镜合教授根据长期临床实践选用的一种起效快、以攻为主、攻补结合的中药复方制剂。该方以甘遂祛经隧水湿，大朝泄脏腑水湿，芫花消胸胁伏饮痰癖。又配以具苦降辛散之性的葶苈子清热平喘、利水消肿。由于上述诸药药性峻烈，故配以甘温之大枣，既甘温调补脾胃，又缓和峻药之性，共奏攻补兼施之功。鉴于CHF主要治疗手段为强心利尿，本方故使用强心作用明显的葶苈子与利尿作用明显的十枣汤相配合，展开对CHF的临床与实验观察，以期能为中医临床心衰急救提供一种有效的中药复方制剂。二、临床研究 采用随机分组法，单盲试验。共确定中药观察组32例，西药扣例。停用强心、利尿、扩血管西药1周。中药组清晨予大枣汤 （大枣309水煎）送服，下午予茸苗子309水煎送服。另外甘遂、大朝、芜花三味醋制后研末，于第1、3、5、7天清晨空腹大枣汤送服，剂量从各屹起用，以每天下利5—7次为度，7天为1个疗程。西药组予地高辛 0．！254．25mg qd、速尿 20mg bidrtid口服，7天为1个疗程。治疗前后均测定自由基三项、微量元素、甲皱微循环检查等各项观测指标以及心衰积分、中医自觉症状的改善情况等。治疗前后各项指标的统计应用T检验及X‘检验。 结果表明；①该方对CHF的治疗总有效率可达75％，并可有效地降低心衰积分值，对CHF患者存在的不同程度的主述，也有明显的改善作用。②中药组与西药组对心衰病人均有较好的疗效，但中药组对阳虚水泛型及心肾阳虚型两型疗效较好，而对气虚血瘀型及心气阴虚型疗效不理想。＠中药组可提高患者Zn、Fe、Mg、Cu等元素含量，降低Ca”含量。对于甲皱微循环检查，中药组对形态积分、流态积分、管周状态积分、总积分等均有一定程度的降低作用。而对于自由基三项，中药组可提高SOD、GSHPX酶活力，降低LPO产物的聚积。三、实验观寨 新西兰雄性兔20只，体重2．5刁kg，随机分为四组：对照组、中药组、中西药组、西药组。分离兔右颈总动脉，然后用介入法造成兔超容量负荷型心衰模型，抽血检查并根据生理记录仪的波形前后记录并计算主动脉收缩压旧BPL 主动脉舒张压（DBP＊左心室收缩压（LVSP）、左心室舒张压（LVDP）、左室内压最大上升速率（LV＋dp用tX左室内压最大下降速率（LV—dp／d）等值。然后留置4F、SF头皮针管。造模成功后，按折算剂量分别予以灌胃，对照组灌等量蒸馏水，连灌1周。第8天，麻醉兔后重新打开伤口，原法抽血化验，并测量上述各值。血标本离心后送检自由基、微量元素等指标。解剖兔心脏固定后送校病理教研室病检，并描记典型病理图像。 结果表明：①造模后各组 y、SBP、LVSP、LV＋dP／dt及 LV一dp／dt均有不同程度下降，而LVDP却有显著提高。另外，对照组经过安慰治疗，各项指标无明显变化，而其余三组 LV＋dp／dt、LV 48一dp／dt均有改变，中药组及中西药组LVDP也有明显F降。体重?更多还原

【Abstract】 Part I .General IntroductionCongestive heart failure (CHF) is one of the common dangerous diseases in internal medical system with high clinical death rate.Companying with the improvement of people’s living condition and the changing of diet structure ,the incidence of CHF increases rapidly now.Usually western medicine is used to control CHF with the therapeutic principle of lightening the load of the heart and increasing the myocardial contractility. And the using of cardiocinetic and diuretic is the customary treatment. But these drugs have many side-effects, such as leading imbalance of electrolyte and acid-base ,causing disturbance of hemodynamics and inducing digitalis poisoning.Some of them can even worsen the patient’s condition. All these makes the treatment very difficult and complicated.CHF belongs to palpitation,edema,dyspnea,cardiac bi-syndrome and phlegm-retention due to the theory of TCM.And it happens because of long distance of disease,deficiency of heart-energy,heart-yang,heart-blood and heart-yin or incoordination between the solid and hollow organs.Chinese patent medicines are also used in treating CHF recently, including clinical and experimental studies.simple recipe and complex prescription studies ,pure Chinese medicines studies.combined Chinese and western medicines studies , good treatment effects are acquired. But the effects of these chosen Chinese medicines are partial to warm and inrigorate, so they need long course of treatment. Some of the clinical design is not scientific enough, and has unstable therapy effects.ShiZao decoction(SZD) is one of the famous recipe in Treatise on Exogenous Febrile Diseases. In Zhang ZhongJing’s original assay it treats the fluid-retention syndrome in the thorax, marked by distension and pain over the hypochondriac region, which is aggravated by52coughing , spitting .moving and breathing , accompanied with retching, shortness of breath, sunken and wiry pulse. But no treatment of CHF is reported . Semen Lepidii Seu Descurainiae(SLD) can eliminate phlegm, promote diuresis and relieve dyspnea. Its alcohlic extract acting as cardioglycosides ,can emhances myocardial contractility, slows heart rate and decreases the conduction rate in experimental animals. But the effective composition of SLD is very low in itself, which needs more dosage to take effect.The recipe of SZD and SLD is a complex Chinese prescription which takes effect rapidly, acts mostly on eliminating the evils ,treats aiming at both the elimination of evils and the restoration of healthy energy, it is invented by the professor Chen JinHe ,one of the famous experts specialized in combining Chinese and Western medicines. The recipe is composed of Fructus Ziziphi Jujubae,Radix Euphorbiae Kansui, Radix Euphorbiae Pekinensis, Flos Genkwa and Semen Lepidii Seu Descurainiae, whose effect can enhance myocardial contractility and diuretic . We hope that a new complex Chinese prescription could be found to treat clinical emergency by developing clinical and experimental studies on this recipe .Part II. Clinical StudiesRandomize and single-blind are adopted to study 62 patients, in which 32 belong to Chinese observation group, and 30 belong to Western medicine group. The Chinese observation group is given the recipe of SZD and SLD for one week ,whereas Digoxin and Furosemide are taken to the other group. Both group measure the quotas of free radical,trace element and nail fold microcirculation before and after the studies, and all the quotas are calculated with T-test or X2 -test.The result means: (l)the recipe’s total effective rate is 75%,and it can improve many symptoms ,such as palpitation ,edema, dyspnea ,anorexia and abdominal flatulence. (2)the Chinese medicine group’s suitable syndrome types of TCM are retention of fluid caused by Yang-deficiency and Yang-deficiency of both heart and kidney .But its effect to blood stasis due to deficiency of Qi and deficiency of both heart Qi and yin is unreliable. (3) The group of Chinese medicine can improve the content更多还原