论文标题:开心胶囊Ⅰ号对心力衰竭大鼠心肌细胞凋亡调控作用的实验研究
The Experimental Study of Kaixin I Capsle on Cardiomyocyte Apoptosis in Experimental Heart Failue Rats
论文作者 赵锋利
论文导师 陈镜合,论文学位 硕士,论文专业 中医内科学
论文单位 广州中医药大学,点击次数 67,论文页数 102页File Size3217k
2000-05-01论文网 http://www.lw23.com/lunwen_327512917/ 开心胶囊Ⅰ;心力衰竭;细胞凋亡; 一氧化氮;内皮素
KAIXIN I capsule;Nitrogen monoxide (NO); Endothelins(ET);Heart failure(HF) apoptpsisx
心力衰竭（Heart Failure简称HF）是严重危害人类健康的一种病理综合征，见于各种心血管疾病。心力衰竭患者一旦出现典型症状，病情将进行性加重，死亡率与恶性肿瘤病人相仿。 开心胶囊Ⅰ号是广州中医药大学第一附属医院陈镜合教授研制的中药复方制剂，临床上用于治疗无症状性心力衰竭及心功能尚属NYHAⅠ、Ⅱ级的轻度心力衰竭患者，疗效显著。为了深入阐明验方开心胶囊Ⅰ号的机理，本研究从文献理论与动物实验两方面入手做了以下工作： （一）文献研究1.医文献理论方面：传统中医学无明确的心衰病名，一般将本病归于“喘证”“心悸”“水肿”等范畴，认为其基本病机是水气与气（阳）虚，治疗上偏重补虚与治水。现代中医学已明确认识到本病，但病名尚无共识之称谓，病机方面认为其主要是心气虚、血瘀、水泛三者病变的相互转化；治疗上多联合应用益气、温阳、化瘀、利水等四种基本治法，不同病情，不同医家，各有侧重；某些情况下，心衰的中医药疗法与现代西医疗法优势互补。2.现代医学文献理论方面：经复习文献后认为：A.近年来世界心血管病学界在HF治疗策略上的最重要转变是：维护心脏、提前治疗尚未出现明显“充血性”症状的HF，以改善患者生活质量、提高远期存活率为根本目标。B.在HF概念方面的重要转变是：提出了无症状性心力衰竭（AHF）。AHF是指已有心脏压力升高，但既无典型症状也无明确体征的HF亚临床阶段。AHF是比心力衰竭NYHAⅠ级更为轻浅的阶 开心欣辽1号对心力衷场大辽妇胞凋亡训扭作用的实脸研兑段，表面上病情稳定，但内部心肌重构与心脏重塑等病理生理变化持续进展，适应状态迟早会变转变为适应不良而发展成有症状心衰。C．在11卜基础研究方面，认为现在更注重阶发展演变这一动态进程的病理生理机制。己有大量证据说明：HF的进展与以下三方面关系密切：①血流动力学异常②神经内分泌的激活③心脏重塑。三者互为因果，形成恶性循环。HF病程进展的分子细胞学基础被认为主要是：①心肌细胞的变化②心肌细胞外间基质细胞的纤维化，其中心肌细胞的变化又包括心肌细胞数量和质量的变化两方而（坏死与凋亡同时存在，并且适应不良性肥大）。 据此，在中医学“不治己病治末病”的理论指导下，以现代医学细胞凋亡与神经内分泌两方面的成果为研究切入点，对开心胶囊1号的疗效机制进行动物实验研究，探讨其与凋亡、凋亡基因及一氧化氮、内皮素的相关机制。 （二）实验研究1．动物模型的建立： 本研究以结扎左冠状动脉主干下2．4mm所致大鼠MI后模型作为心衰模型。 造模成功后三天的SD大鼠140只（假手术组只开胸不结扎冠状动脉人雌雄谷半u50＜100g人 随机分为 5组，每组各 20t2只。开心胶囊 1号高、低剂量组，分别以开心胶囊 1号灌胃（10、sn·kg‘·d－‘）；卡托普利组以自由饮水给药门·L－＼ 模型组、假手术组正常喂养。连续给药8周后开胸，心脏取血后，取心脏，部分非梗塞心肌剪成小块分别放液氮中保存，部分心脏 10yo甲醛固定包埋后平行于乳头肌水平取片，血标本离心后－20oC保存。待测下列指标。2 尤衍利硕士论文 导师：际似合被投 2．对HF大鼠血清及心肌NO的影响： 按试剂盒要求以硝酸还原酶法，通过分光光度计测定NO水平。 结果表明开心胜囊1号可增加血清m浓度，但与模型组及假手术组 比较无统计学意义（卜＞0．（）5）。模型组心肌NO浓度较假手水组增加 （卜＜O．05）：开心胶囊1号高剂量组能增加心肌洲浓度，与模型组比 较差异显著（P＜（）．05）。 人 对仰大鼠血浆及心肌盯的影响： 按试剂盒要求应用放射免疫法测定ET结果表明，模型组血浆及 心肌 E＊较假手术组明显增高，差异非常显著（P＜0．00）：升心胶囊 I号高、低剂量组较模型组减少，差异非常显著（P＜0．（）of，（）．of）。 4．对＊‘人鼠心肌细胞凋亡的影响： 按试剂盒要求应用TUNEL法检测HF大鼠左室梗塞周围心肌细胞 结果表明，模型组凋亡指数较假手术组增加（V0．05）：开心胶囊1 号高剂量组较模型组减少（P＜0．05）。 5．对 HF大鼠心肌细胞 bC－2、P53蛋白表达的影响： 按试剂盒要求应用叩免疫组织化学法检测心肌细胞卜C卜2蛋白 表达结果表明，模型组表达较假手术组增加叩N．00）；开心胶囊 1 号高剂量组较模型组增多（P＜0．05）。各组 PS：1蛋白表达未能显示阳 性结果。 开心胶囊1号临床上应用可能对延缓心衰进展有利，可防治AHF、 NYHA、U级患者由适应发展至适应不良。据动物实验，推测其疗效 机理可能与其具?
Heatt Failure (HF) is a common and serious clinical s~ndtone that deadly impairs people? s health. It is not a single disease, but the final stage of all kinds of cardiac desease. Its morbidity is high, and its surviral rat within five years is similar to that of malignant tumor. It is very important to defend the health of human being k inquiring into the pathologic mechanism and finding the ways for treat ing CE-fF. ha ix iii i capsule is the pat ient medicine iit~ented by Pt o. Clien. j inghe of the First Atfi I iated Hospital of Guangzhoii Uni ~ts it v of ThM, wh icli is clinical lv used to cu~ e the asyrnptomat ic tteurt ta i lure and HF patient of NYHA I or II ,and have very good effect. In order to prove the mechmtisw of it? s good effect, we did some research from t~o big aspect, the theory research and the animal experiment: the theory research 1. the theory research of TCM in HF There is not a identical conclusion about the name, pat.hogenesis and treatment for CHF in traditional Chinese medicine (TCM). Generally it is iiicltided in such categosies as syndrone of dyspnea, palpitation, edema and so on. It is considered that the basic pathogenesis of CHF is blood stasis due to deficiency of qt and edema due to deficiency of yang. Deficiency of qi and yang is the origin, which blood stasis and edema are the superficiality. It involvesthe four organs: heart, kidney, lung aad spleen. The basis principle of treatment is supplementing qt, activating blood circulation, invigorating yang and dimes is. 2. the theory research of West梞edicine in HF: A. The strategy of curing HF of the world has change as this : safeguard the heart, real the HF pitt iettt befox e the congest rye semiotic has appeared , with the ultimate target of better-went of the quality of living, prolong the livability of the patients. B. A twpot tant transit ion of the HF conception is asymptomat.ic heart failure? s appearance (AHF). AHF means that a patient who has had the hoist of the LVEDP ,but has none symptom. AHF is the stage more lighter than the HF NYHA I. The state of this disease looks very stable, but it.? s a fakement. Actually , thete are a lot of pathiophystologtcal changes evolving at this state such as entricular 5 ~fr~5:. I 4i~5iUML-~5 t~5 ~?1~ 閪 remolding and myocardial remolding. It will soon or later translate into congestive heart failure. C. The definite pat.ho~)hysiological mechanism of UHF is not very clear yet. Now it. is considered that the main reason that causes UHF to be exacerbated from adaptation to maladjustment is the decrease in amount and the change of quail ty (structure and funct ion) of iuyocardial cells due to maiiv different reasons. The latest study found that apoptosis is one of the reasons that cause the decrease of myocardial cells and decline in the function of cardiac muscle. Recently the modern medical treatments for CHF have dcvel~ped from traditional methods, such as diuresis, dilatating !)lOOd vessels, using cardiot.onic and so on to many other ways, such as arousing negative inot.ropic action, antagonizing neurohormone, iiihibi t ing ventricular restructure and apoptosis of myocardial cells and so on. According to study of the above, we decide to use the achievement of apoptosis and neuroendocrine theory in the HF and do the experiment that can prove the
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