【作者】 周迎春；

【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】 心肌梗塞（myocardial infarction，MI）后心室重构（ventricularremodelling，VR）系指MI后梗塞区和非梗塞区心室几何构型的改变。据统计发生率为30％—50％。VR往往表现为一种不断发展的过程，是远期发生心脏性死亡的最重要的危险因素之一。因此多数学者认为MI新的治疗目标应是抗重塑（antiremodelling）。研究表明，肾素-血管紧张素系统（renin-angiotensin system，RAS）的自分泌和旁分泌在左室重构中可能起着关键的不良调控作用。其中血管紧张素Ⅱ（angiotensin Ⅱ，Ang Ⅱ）可能是一系列生化反应的核心。其作用通过AT₁受体介导。目前在MI后应用中医药改善左室重构的研究近乎缺如。系统地研究和探讨MI后左室重构的发病机制，进一步完善祖国医学理论，开发新的抗重塑中药制剂，具有重要意义。 本文通过回顾历代文献，总结近年来中医药对本病的研究进展及导师多年经验，认为本病属中医胸痹心痛、真心痛等病范畴，MI后左室重构主要病机为气阴亏虚，痰瘀气滞。开心胶囊是以生脉散、失笑散、越鞠丸加减而成的导师经验方，临床研究证明该方对防治MI后心室重构有效。本研究以开心胶囊防治结扎左冠状动脉主干所致大鼠MI后左室重构，并探讨其与Ang Ⅱ相关的机制。 造模成功后三天的SD大鼠140只，雌雄各半，（250-300g），随机分为5组，每组各20-22只。开心胶囊高、低剂量组，分别以开心胶囊灌胃(10、5g·kg^-1·d^-1)；开搏通组以自由饮水给药(lg·L^-1)；心肌梗塞组、假手术组正常喂养。连续给药8周测定心功能后开胸，心脏取血 开心胶羹抗人鼠心肌幢宗后心室觑构的实验研究3后，取心脏，称重及左室重，部分非梗塞心肌剪成小块分别放液氮中保存，部分心耻甲醛固定包埋后平行于房室沟自心底至心尖每隔1．5上共取片 4张，血标本离心后．20 OC保存。待测下列指标。一、开心胶羹对大鼠心梗后左室形态的影响 心室构型及心肌细胞重构是造成MI后心功能恶化的重要因素之一。本实验探讨了 MI周后大鼠心脏构筑及开心胶囊对其影响。全自动图像分析系统分析结果表明：平均周长法测定四组梗塞范围分别为人室周长的36．52土3．24％、38．14土4．07％、37．49土4．19％、37l 土3．37％，组间比较无显著性差异o＞0．05卜 MI组心脏指数、左心腔面积均值、MI区室壁变薄比、室间隔横截面积、室间隔厚度较假手术组明显增高炉＜0．of)，而开心胶囊高、低剂量组及开搏通组各项指标较MI组明显降低 （P＜o．m，o．05人证明心梗可导致心脏构型改变，开心胶囊可以抗心梗后心室重构。二、开心肢羹对大鼠心梗后左室非梗塞区胶原改建的彤响 胶原过度沉积会使心肌僵硬度增加，影响心脏功能。而胶原损伤不仅与胶原总量有关，胶原的型别、如何交织和交织的量和类型与胶原的正常功能的维持也有很大关系。本文用羟脯氢酸法及苦味酸天狼星红－偏振光方法结合图象分析，观察了开心胶囊对心梗后大鼠非梗塞区左室心肌胶原总量及类型和分布状态的影响。结果提示，MI组大鼠左室非梗塞区胶原总量门3．33上4．38ug／mg）及 1型及＊！型胶原比值O．58土0．86)显著增高，与假手术组比较差异非常显著（P＜0刀1）。开心胶囊高、低剂量组胶原总量（22．87士3．34、27＊ 土4．08ug／mg）及 1／Ill＊值 ＊．96士0．61、8．24上0．41)较梗塞组降低(Prto．of人与开搏通疗效相近。说明其可以抑制1型胶原蛋白的合成，改变胶原蛋白的构成比，增加心肌顺 研究生：剧迎评 牙师：陈镜O4应性。三、开心地羹对大鼠心梗后心脏功能的影响 梗塞后左室构型改变，心肌细胞肥厚，细胞外基质－胶原网的量和组成的变化可以导致心脏功能减退而影响预后。本实验采用M－6000型生理记录仪测定了开心胶羹较长期应用对MI大鼠心功能的影响。结果表明MI组较假手术组LVSP（115．90ti3．ollnlnHg）、＋dp／dt。x（2510．001472．46mmHg）明显降低（Prto．of，0．05），LVEDP（6．5土2．84InmHg）明显增加（P＜0．05）。开心胶囊高剂量组与梗塞组比较＊卯（125．卯士6．44InlnHg）、＋dP／dt。x（3680．00i795．54llunHg）明显升高（P＜0．of，0．05），LV EDP（6．5土2．8小m们召）明显降低（P＜o．os）。可改善大鼠＊！后8周左室收缩和舒张功能。开搏通以改善舒张功能为主。四、开心胶羹对大鼠心梗后血日紧张素11、醛固国的彤响 心肌梗塞后 RAS系统激活，促进心血管重构，Aug 11是该系统的重要生物活性肽。本实验用放射免疫法观察了开心胶囊对循环和心肌局部Ans11、醛固酮的影响。结果表明，梗塞组与假手术组比较血清和心肌局部Ansl！（2767．13士1696．sins／ml、876．82土273．80us／s）和醛固酮（498．85土132．53gg／ml、1127．63土521．59mm／m）明显增高（P＜0．of）。开心胶囊高低剂量组血清Aug 11（1249．68土1035．58ng／ml、1300．22土716．49us／ml）和醛固酮(243．03土5更多还原

【Abstract】 Ventricular remodelling(VR) following myocardial infarction (MI) is defined as changes in shape and size of the ventricle following acute myocardial infarction. Statistics suggested that its incidence rate was 30%-50%. VR is always a progressive process and it is one of the most important causes of death of later cardiac disease, so most scholars think that the new treat on MI should be antiremodelling of Ventricular. Reseaches showed that autocrine and paracrine of Rennin-angiotensin system(RAS) probably has an important reverse regulation on the left ventricular remodelling and Angiotension II (Ang II), may be the core of a series of biochemical reactions, is working by ATi receptor. There is no study on treatment on left ventricular remodelling following MI with traditional Chinese medicine (TCM). It has a great significance that we take systematic researches on the mechanisms of left ventricular remodelling following MI in order to improve the theory of traditional Chinese medicine and exploit new traditional Chinese medicine.VR following MI belongs to xiongbi, xintong and zhenxintong in TCM. The main mechanisms are deficiency of qi and yin, stagnancy of phlegm and qi. Kaixin capsule II is a recipe made by my teacher on his experience. It consists of the main components of shengmaisan, shixiaosan zndyuejuwan. It had been proved to have effective treatment on VR following MI. The effect of Kaixin capsule and Ang II were researched on the disease model of left ventricular remodelling which was made by ligating rat’s left coronary artery.50 SD rats, half male and female, were randomly divided into 5 groups (n=10). From the third day on after the model was finished, high dose Kaixin capsule group and low dose Kaixin capsule group was respectively received Kaixin capsule lOg-k^.d"1 and 5 g-k^.d"1 . Captopri group was received Captopri in water. MI group and pseudooperation group were feed normally. 8 weeks later, we measured cardiac function, sucked out the blood in hearts then weight the hearts and left ventriculars. Some of the hearts no MI were sect into fragments and stored in liquid nitrogen, the others were sliced four times every 1.5-2mm from basis cordis to cardiac apex, which paralleling atrioventricular sulcus after being fixed up with formaldehyde and embeded. The blood was stored at -20 *C after centrifugation.1. The effect of Kaixin capsule on the shape and function of left ventricle following MI in rats.Remodelling of ventricular and myocardial cell following MI was one of important factors in deterioration of cardiac function. We investigated cardiac construction and the effect of Karxin capsule on it. The sizes of MI in four groups were respectively 36.52?.24, 38.14+4.07, 37.49?.19, 37.16?3.57,which was calculated by the average circulation method, there is no significant difference (P>0.05) among them. The cardiac index, mean of area in left cardiac cavity, area and depth of interventricular septum were all significance increased in MI group compared with pseudooperation group(P <0.01), but these values of high dose and low dose Karxin capsule groups were decreased compared with these of MI group. It was proved that Kaixin capsule could restrain the dilation and hypertrophy of left ventricular and had beneficial effect on ventricular remodelling following MI, if being used for a long time.2. The effect of Kaixin capsule on collagen reconstruction in non-infarcted zone of left ventricular.Collagen’s over-sedimentation can make myocardial harden which affects cardiac function. Damage of collagen relates to not only its amount, but also its type and distribution. We observed the effect ofKaixin capsule on the total amount, types and distribution of myocardial collagen in non-infarcted segments of left ventricle in rats by combining the method of hydroxyproline and Sirius Red F 3B 200 with image analysis. The results showed that both the myocardial collagen’s total amount(33.33?.38) and the rate of collagen I/collagenIII(9.58?.86) increased sign更多还原