参元丹择期PCI围手术期心肌保护作用及其对EPCs动员与归巢影响研究

发布时间：2018-06-21 05:07

本文选题：参元丹 + 经皮冠状动脉介入治疗　；参考：《北京中医药大学》2017年硕士论文

【摘要】：目的:观察参元丹(SYD)对非ST段抬高急性冠脉综合征(NSTE-ACS)患者择期PCI围手术期心肌损伤(PMI)的干预效果及其机制探索。方法:本课题采用随机、双盲、安慰剂、对照的观察方法,研究对象均为首都医科大学附属北京中医医院心血管科2016年7月至2016年12月拟行冠状动脉介入(PCI)治疗的,中医证型属气虚血瘀证的NSTE-ACS患者。最终68名符合纳入标准的患者被随机分为参元丹组(n=36)和安慰剂组(n=32),受试者在接受冠心病常规药物治疗基础上,于术前3天至术后7天根据分组情况服用参元丹或安慰剂,并根据患者具体病情择期行PCI治疗。临床观察包括:(1)术前、术后4h、术后24h及术后7d心肌损伤标志物cTNT、CK-MB的变化;外周血EPCs计数;促血管内皮生长因子VEGF、SDF-1水平变化;氧化应激指标SOD、MDA的变化;炎症反应指标hs-CRP、IL-6的变化;(2)术前、术后24h行彩色多普勒超声及速度向量成像技术(VVI)检测;(3)术后30天MACE事件(4)安全性监测。结果:(1)基线情况:参元丹组与安慰剂组纳入患者各方面基线资料(一般情况、各指标术前水平等)均无统计学差异(P0.05),具有可比性。(2)PMI发生率:参元丹组PMI的发病率(2.8%)低于安慰剂组(21.9%),两组具有统计学差异(P0.05)。(3)CK-MB水平检测:参元丹组术后4h、24h,安慰剂组术后4h、24h、7d比较各组术前CK-MB水平均升高(P0.05),差异均具有统计学意义。参元丹组术后7d较术前有升高趋势(P0.05),差异不具有统计学意义。两组术后4h、24h、7d的CK-MB水平比较,参元丹组均有低于安慰剂组趋势,但差异不具有统计学意义(P0.05)。(4)EPCs动员相关:①EPCs计数:参元丹组术后24h、7d比较术前外周血EPCs水平均升高(P0.05),差异具有统计学意义。参元丹组术后4h、安慰剂组术后4h、24h、7d比较各组术前有升高趋势(P0.05),差异不具有统计学意义。参元丹组术后24h、7d高于安慰剂组同时间点(P0.05),差异具有统计学意义。两组术后4h比较,参元丹组有高于安慰剂组趋势(P0.05),但差异均不具有统计学意义。②VEGF水平:参元丹组术后24h、7d,安慰剂组术后24h比较各组术前外周血VEGF水平均升高(P0.05),差异具有统计学意义。参元丹组术后4h、安慰剂组术后4h、7d与各组术前比较(P0.05),差异均不具有统计学意义。参元丹组术后24h、7d均有高于安慰剂组同时间点趋势(P0.05),两组术后4h比较(P0.05),差异均不具有统计学意义。③SDF-1水平:参元丹组术后24h较本组术前外周血SDF-1水平升高(P0.05),差异具有统计学意义。参元丹组术后4h、7d,安慰剂组术后4h、24h、7d与各组术前比较(P0.05),差异不具有统计学意义。参元丹组术后24h、7d均高于安慰剂组同时间点(P0.05),差异具有统计学意义。两组术后4h比较,差异不具有统计学意义(P0.05)。④相关性:参元丹组PCI术前,PCI术后4h、24h、7d外周血EPCs及VEGF水平存在显著相关关系(r=0.231,P0.05);参元丹组PCI术前,PCI术后4h、24h、7d外周血EPCs及SDF-1水平存在显著相关关系(r=0.323,P0.05)。(5)炎症因子相关:①hs-CRP水平:两组术后24h较各组术前hs-CRP水平均升高(P0.05),差异具有统计学意义。参元丹组术后4h、7d,安慰剂组术后4h、7d与各组术前比较(P0.05),差异均不具有统计学意义。两组术后7d均低于各组术后24h(P0.05),差异具有统计学意义。参元丹组术后4h、24h、7d均有低于安慰剂组同时间点的趋势(P0.05),但差异不具有统计学意义。②IL-6 水平:参元丹组术后24h、安慰剂组术后4h、24h比较本组术前IL-6水平均升高(P0.05),差异具有统计学意义。参元丹组术后4h、7d,安慰剂组术后7d与各组术前比较(P0.05),差异均不具有统计学意义。参元丹组术后4h、24h、7d均有低于安慰剂组同时间的趋势(P0.05),但差异均不具有统计学意义。(6)氧化应激相关:①SOD水平:安慰剂组术后24h低于本组术前SOD水平(P0.05),差异具有统计学意义。参元丹组术后4h、24h、7d,安慰剂组术后4h、7d比较各组术前,均无统计学差异(P0.05)。参元丹组术后24h高于安慰剂组术后24h(P0.05),差异具有统计学意义。参元丹组术后4h、7d均有高于安慰剂组同时间的趋势(P0.05),但差异均不具有统计学意义。②MDA水平:两组术后24h较各组术前MDA水平均升高(P0.05),差异具有统计学意义。参元丹组术后4h、7d,安慰剂组术后4h、7d比较各组术前,均无统计学差异(P0.05)。参元丹组术后4h、24h、7d均有低于安慰剂组同时间点的趋势(P0.05),但差异均不具有统计学意义。(7)超声心动及WI技术相关:①参元丹组PCI术后24h的左室射血分数、左室舒张末径及E/A值比较术前均未发生具有统计学意义的变化(P0.05)。②安慰剂组PCI术后24h的前间隔心尖段、前壁心尖段、前壁基底段、下壁心尖段、下壁中间段的应变指标低于本组术前水平(P0.05),差异具有统计学意义;PCI术后24小时参元丹组与安慰剂组比较,在前间隔心尖段、前壁心尖段、下壁心尖段参元丹组应变指标改善情况优于安慰剂组(P0.05),差异具有统计学意义。③安慰剂组PCI术后24h的前间隔心尖段、前壁心尖段、下壁心尖段、下壁中间段应变率指标低于本组术前水平(P0.05),差异具有统计学意义;PCI术后24h参元丹组与安慰剂组比较,在前间隔心尖段、前壁心尖段、下壁心尖段,参元丹组应变率指标改善情况优于安慰剂组(P0.05),差异具有统计学意义。(8)MACE事件及安全性监测:两组间比较,参元丹组术后30天MACE事件发生率(5.6%)有低于安慰剂组(15.6%)趋势,但差异不具统计学意义(P0.05);试验期间无参元丹相关的不良反应发生,安全性良好。结论:(1)SYD能降低NSTE-ACS患者PMI发生率,并具有降低PCI围手术期血清CK-MB水平、减少PCI术后30天MACE事件发生率趋势,且安全性良好,提示SYD对NSTE-ACS患者PCI围手术期有一定心肌保护作用。(2)SYD可增加NSTE-ACS患者择期PCI围手术期外周血EPCs、VEGF及SDF-1水平,提示SYD具有改善NSTE-ACS患者择期PCI围手术期EPCs动员与归巢作用,其机制可能与上调外周血中VEGF和SDF-1的表达来实现,这也可能是改善NSTE-ACS患者PCI围手术期心肌损伤的机制之一。(3)SYD具有降低NSTE-ACS患者择期PCI围手术期血清炎症反应因子hs-CRP与IL-6水平趋势,提示SYD对NSTE-ACS患者择期PCI围手术期心肌保护作用可能与其抑制炎症反应相关。(4)SYD干预NSTE-ACS患者择期PCI围手术期,可抑制PCI术后SOD水平的降低,并具有抑制PCI术后MDA水平升高趋势,提示SYD对NSTE-ACS患者择期PCI围手术期心肌保护作用可能与其抗氧化应激作用相关。(5)应用VVI技术分析节段室壁收缩功能的变化,以节段心肌应变及应变率为效应指标,发现参元丹组节段室壁运动与安慰剂组比较有一定改善,也提示VVI相较于传统超声心动更有助于PMI的早期评估。综上所述:SYD对NSTE-ACS患者择期PCI围手术期具有一定心肌保护作用,其机制可能与促进EPCs动员与归巢、抑制炎症反应及抗氧化应激作用相关。
[Abstract]:Objective: To observe the effect and mechanism of Shen Yuan Dan (SYD) on PCI perioperative myocardial injury (PMI) in patients with non ST segment elevation acute coronary syndrome (NSTE-ACS). Methods: a randomized, double blind, placebo-controlled, controlled study was used in this study, and the study on the cardiovascular department of Beijing Chinese Medicine Hospital affiliated to Capital Medical University 2016 From July to December 2016, the TCM syndrome type was NSTE-ACS patients with Qi deficiency and blood stasis syndrome. The final 68 eligible patients were randomly divided into the Shen Yuan Dan group (n=36) and the placebo group (n=32). The subjects were treated on the basis of the conventional medicine treatment for coronary heart disease (CAD), and were divided into groups from 3 days before the operation to 7 days after the operation. Taking Shen Yuan Dan or placebo and PCI treatment according to the specific condition of the patient, clinical observation included: (1) preoperative, postoperative 4h, postoperative 24h and postoperative 7d myocardial damage markers, cTNT, CK-MB, peripheral blood EPCs count, vascular endothelial growth factor VEGF, SDF-1 level changes, oxidative stress indicators SOD, MDA changes; inflammatory response indicators Changes in hs-CRP and IL-6; (2) preoperative and postoperative 24h color Doppler ultrasound and velocity vector imaging (VVI) detection; (3) MACE event 30 days after operation (4) safety monitoring. Results: (1) baseline situation: the baseline data (general condition, preoperative level, etc.) of the Shen Yuan Dan group and the placebo group were not statistically different (P0.05), (2) the incidence of PMI: the incidence of PMI in the Shen Yuan Dan group (2.8%) was lower than that of the placebo group (21.9%), and the two groups had statistical difference (P0.05). (3) CK-MB level test: 4h, 24h, 4h, 24h, 7d in the placebo group after operation, 4h, 24h, 7d were all increased (P0.05) in all groups before operation (P0.05), and the difference was statistically significant. After the operation of Shen Yuan Dan group, 7d was compared The difference was not statistically significant before operation (P0.05). The CK-MB level of 4h, 24h, 7d in the two groups was lower than that of the placebo group, but the difference was not statistically significant (P0.05). (4) EPCs mobilization correlation: (1) EPCs count: 24h in the group of Shen Yuan Dan group after operation, 7d compared with the EPCs level of peripheral blood before operation (P0.05), the difference Statistical significance. 4h after operation in the Shen Yuan Dan group, 4h, 24h, 7d after operation in the placebo group compared with each group before operation (P0.05), the difference was not statistically significant. The 24h in the Shen Yuan group after operation, 7d was higher than the placebo group at the same time point (P0.05), the difference was statistically significant. The two groups after the operation 4H compared to the placebo group was higher than the placebo group trend (P0.05) But the difference was not statistically significant. (2) VEGF level: after the operation of 24h, 7d, and 24h in the group of Shen Yuan Dan group, the level of VEGF in the peripheral blood increased (P0.05) before the operation of the placebo group (P0.05), the difference was statistically significant. After the operation of the Shen Yuan Dan group, 4h, 4h, 7d and the preoperative comparison of each group (P0.05) were not statistically significant. After the operation, 24h, 7d were higher than the placebo group at the same time point trend (P0.05), the two groups after the 4H comparison (P0.05), the difference was not statistically significant. (3) SDF-1 level: after the operation of the Shen Yuan Dan group, 24h was higher than the level of SDF-1 in the peripheral blood (P0.05) before the operation of the group (P0.05), the difference was statistically significant. After the operation of Shen Yuan Dan group, 4h, 7d, placebo group after operation 4H Preoperative comparison (P0.05) was not statistically significant. 24h, 7d in the group of Shen Yuan Dan group were higher than that in the placebo group at the same time point (P0.05), and the difference was statistically significant. The difference between the two groups was not statistically significant (P0.05). (P0.05) correlation: there was a significant phase in the 4h, 24h, 7d peripheral blood EPCs and the level of 7D peripheral blood before the operation of PCI in the group of Shen Yuan Dan group. Relationship (r=0.231, P0.05); before PCI in Shen Yuan group, there was a significant correlation between EPCs and SDF-1 levels in 4h, 24h, 7d after PCI (r=0.323, P0.05). (5) correlation of inflammatory factors: (1) hs-CRP level: the two groups were higher than each group before operation, and the difference was statistically significant. 4h, 7d and each group preoperative comparison (P0.05), the difference was not statistically significant. The two groups after the operation of 7D were lower than 24h (P0.05) after the operation, the difference was statistically significant. After the operation, 4h, 24h, 7d were lower than the placebo group at the same time point (P0.05), but the difference was not statistically significant. After the operation, 4h, 24h compared with the average increase of IL-6 water (P0.05) before operation (P0.05), the difference was statistically significant. The difference was not statistically significant between the 4h, 7d and placebo group after operation (P0.05) after operation in the group of Shen Yuan Dan group (P0.05), and there was a trend of 4h, 24h, 7d after the operation of the Shen Yuan Dan group. (6) oxidative stress correlation: (1) SOD level: 24h in placebo group was lower than before operation SOD level (P0.05), the difference was statistically significant. 4h, 24h, 7d, 4H in placebo group after operation in the group of Shen Yuan Dan group, 7d compared to each group before operation, no statistical difference (P0.05). Statistical significance. 4h, 7d after the operation of the Shen Yuan group were higher than the placebo group at the same time (P0.05), but the difference was not statistically significant. (2) MDA level: 24h after operation in the two groups increased (P0.05) compared with each group before operation (P0.05), the difference was statistically significant. After operation of the Shen Yuan Dan group, 4h, 7d, placebo group after operation, 4h, 7d compared groups before the operation, all the no group Study difference (P0.05). The trend of 4h, 24h and 7d in the group of Shen Yuan Dan group was lower than that in the placebo group at the same time point (P0.05), but the difference was not statistically significant. (7) the correlation of echocardiography and WI Technology: (1) the left ventricular ejection fraction, left ventricular diastolic diameter and E/A value of the left ventricular diastolic end diastolic diameter and E/A value of the group of Shen Yuan Dan group were not statistically significant before the operation. P0.05. (2) the anterior septal apical segment of the 24h in the placebo group, the anterior apical segment, the anterior wall base segment, the inferior wall apical segment, the inferior wall segment and the lower middle segment were lower than the preoperative level (P0.05), and the difference was statistically significant. 24 hours after PCI, the Shen Yuan Dan group was compared with the comfort group, at the apical apical segment, the anterior apical segment and the inferior wall apex in the anterior septal section. The improvement of the strain index of the Duan Shen Yuan group was better than that of the placebo group (P0.05), and the difference was statistically significant. (3) the pre apical apical segment of the 24h in the placebo group, the apical segment of the anterior wall, the lower wall apical segment, the middle segment of the lower wall of the placebo group were lower than the preoperative level of the group (P0.05), and the difference was statistically significant. The 24h Shen Yuan Dan group after PCI and the consolation of the consolation of the group 24h. The improvement of the strain rate index in the apical apical segment, the anterior apical segment, the lower wall apical segment and the Shen Yuan Dan group was better than the placebo group (P0.05). (8) the MACE event and safety monitoring: the incidence of MACE events at the 30 day after the two groups (5.6%) was lower than the placebo group (15.6%), but the difference was less than that of the placebo group (15.6%), but the difference was less than that of the placebo group. The difference was not statistically significant (P0.05); the adverse reactions associated with no Shen Yuan Dan occurred during the test. Conclusion: (1) SYD could reduce the incidence of PMI in NSTE-ACS patients, reduce the level of serum CK-MB in the perioperative period of PCI, reduce the incidence of MACE events at the 30 day after PCI, and have good safety, suggesting SYD to NSTE-ACS PCI. (2) SYD can increase the level of EPCs, VEGF and SDF-1 in peripheral blood of patients with NSTE-ACS, suggesting that SYD has the effect of improving EPCs mobilization and homing in PCI perioperative period of NSTE-ACS patients. The mechanism may be achieved by up regulation of VEGF and SDF-1 in peripheral blood. One of the mechanisms of myocardial injury during the perioperative period of PCI. (3) SYD has a tendency to reduce the level of serum inflammatory response factors hs-CRP and IL-6 in PCI perioperative period of NSTE-ACS patients, suggesting that the myocardial protective effect of SYD on NSTE-ACS patients may be related to its inhibition of inflammation. (4) SYD intervention NSTE-ACS patients should be selected for PCI perioperative period, It can inhibit the decrease of SOD level after PCI and inhibit the increase of MDA level after PCI operation, suggesting that the myocardial protective effect of SYD on PCI perioperative period may be related to its antioxidant stress. (5) the changes of segmental ventricular wall contraction function are analyzed with VVI technique, and the effect of segmental strain and strain rate is the effect index. The ventricular wall movement in the segment of the Shen Yuan Dan group is better than that of the placebo group. It also suggests that the VVI phase is more helpful to the early evaluation of PMI than the traditional echocardiography. To sum up, SYD has a certain myocardial protective effect on the perioperative PCI perioperative period of NSTE-ACS patients. The mechanism may be related to the promotion of EPCs mobilization and homing, inhibition of inflammatory response and antioxidant activity. Stress related.
【学位授予单位】：北京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R541.4

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