益气逐瘀法干预不稳定心绞痛择期介入治疗围手术期心肌保护研究

Percutaneous coronary intervention (PCI) is gradually becoming the important treatment method for coronary artery disease (CAD) and peri-procedure myocardial injury (PMI) is a complication commonly seen in CAD patients during PCI. There are many studies about reperfusion and no-reflow which cause myocardial injury in patients with ST-elevation myocardial infarction after emergency PCI. But few studies are performed in investigating PMI in patients using selective PCI. Our previous studies supported by NNSF demonstrated that Shen-Yuan-Dan (SYD), a Chinese herbal prescription developed on traditional Chinese medicine (TCM) theory "supplementing qi and pursuing stasis", had the endogenous myocardial protective effects of relieving myocardium injury and improving ischemic reperfusion injury, indicating it may play a role in PMI. Therefore, we plan to perform the following three studies: (1) Investigate the related pathologic mechanisms of PMI in patients with UAP during selective PCI from myocardial injury markers, new ultrasound technology velocity vector imaging (VVI), oxidative and inflammatory angles; (2) Observe the effects of SYD on genes and proteins expression of the key cytokines of oxidative, inflammatory in vivo animal model;(3) In vitro myocardial injury cell model, we determine the effects of SYD medicated serum on genes and proteins expression of NF-κB signal pathway and its downstream key cytokines. The purpose of our study are to systematically illustrate the effects and molecular mechanisms of "supplenting qi and puring stasis" TCM therapeutic method in protection of PMI.

介入治疗（PCI）日益成为冠心病重要的治疗手段，围手术期心肌损伤(PMI)是PCI常见并发症。ST抬高心肌梗死急诊PCI后再灌注及无复流造成的心肌损伤已有较多研究，占PCI主要人群的择期PCI患者PMI研究尚少。我们前一自然基金研究表明，以 "益气逐瘀法"研制的参元丹(SYD)胶囊具有改善心肌缺血，减轻缺血再灌注损伤及促进内源性心肌保护作用，提示在PMI中可能发挥心肌保护作用。本项目(1)随机对照观察SYD对择期PCI患者心肌损伤标志物影响、超声新技术速度向量成像（VVT）观察心功能变化、观察炎症反应与氧化应激细胞因子表达并分析相关机制；(2)在体PMI小型猪模型，观察SYD干预对PMI的影响、炎症反应及氧化应激相关细胞因子基因蛋白表达变化；(3)体外心肌细胞损伤模型，测定SYD含药血清干预后NF-κB信号通路关键调控因子基因蛋白表达；系统阐述益气逐瘀法在PMI中的心肌保护作用及分子机制。

介入治疗（PCI）日益成为冠心病重要的治疗手段，围手术期心肌损伤(PMI)是指与PCI操作相关的心肌细胞微损伤。基于“益气逐瘀法”研制的“参元丹”是首都医科大学附属北京中医医院院内制剂，具有改善心肌缺血、促进内源性心肌保护作用。基于此，课题组在临床研究、动物实验、细胞实验三个层面系统研究益气逐瘀法对不稳定心绞痛择期介入治疗围手术期的心肌保护作用及机制。.临床研究显示：参元丹能够降低术后心肌酶升高程度，降低术后PMI发生率，降低PCI术后MACE事件发生率；能够降低术后TNF-α、VCAM-1、ICAM-1升高程度，减轻PCI术后炎症反应；能够降低术后氧化应激因子MDA、MPO，减轻PCI术后氧化应激反应。.动物实验显示：参元丹能够降低在体PMI小型猪术后心肌酶升高程度；降低术后氧化应激因子MDA、MPO，升高SOD、GSH，并呈剂量相关；降低术后炎症反应因子Hs-CRP、IL-6、IL-10、TNF-α、VCAM-1、ICAM-1基因蛋白表达，减轻心肌局部炎症反应；降低核因子NF-κBp65、pIκB-α的基因蛋白表达，抑制NF-κBp65-DNA结合活性。.细胞实验显示：参元丹干预能够提高大鼠心肌细胞缺氧/复氧模型的存活率、降低LDH、CPK含量，减轻细胞损伤的程度；调节氧化应激因子水平，升高SOD，降低MDA；降低炎症反应因子s-CRP、IL-6、IL-10、TNF-α、VCAM-1、ICAM-1基因蛋白表达；抑制大鼠心肌细胞细胞中NF-κBp65、pIκB-α蛋白表达。.综上，从在临床研究、动物实验、细胞实验三个层面可得出以下结论，参元丹能够降低PCI术后心肌酶升高程度，降低PMI发生率，降低PCI术后MACE事件发生率，减轻炎症反应，调节氧化应激因子，抑制NF-κB信号通路关键因子，提示参元丹能够通过调控氧化应激反应、抑制炎症反应、调控NF-κB信号通路起到不稳定心绞痛择期介入治疗围手术期心肌保护作用。