目的 探讨重组人尿激酶原与替罗非班联用病灶内或冠脉内对ST段抬高型心肌梗死（STEMI）急诊经皮冠状动脉介入治疗（PCI）患者术后心肌微循环、血管内皮功能和血清心肌酶、白细胞介素-18（IL-18）、基质金属蛋白酶-9（MMP-9）、丙二醛（MDA）水平的影响。方法 回顾性选择 2018 年 7 月—2021 年 10 月于合肥市第八人民医院接受急诊 PCI 治疗的 120 例STEMI患者作为研究对象，根据治疗方案不同分为对照组（n＝60）和试验组（n＝60）。其中试验组于病灶内联用重组人尿激酶原与替罗非班治疗，对照组则于冠脉内联用重组人尿激酶原与替罗非班治疗。分别于急诊PCI前后比较两组患者的心肌梗死溶栓治疗（TIMI）血流分级、TIMI心肌灌注分级（TMPG）以及校正TIMI血流帧数计数（cTFC）。记录术后24 h内两组心肌酶［肌酸激酶及其同工酶（CK、CK-MB）、心肌肌钙蛋白T（cTnT）］峰值。分别于急诊PCI术前和术后24 h、7 d时检测两组患者的血管内皮功能指标［内皮素-1（ET-1）、一氧化氮（NO）］以及血清 IL-18、MMP-9、MDA水平。统计两组急诊 PCI术后 6个月随访期间主要不良心脑血管事件（MACCE）发生情况，以及住院期间出血事件发生率。结果 试验组急诊 PCI术后即刻 TIMI 3级、TMPG 3级患者占比（96.67%、95.00%）均显著高于对照组（86.67%、83.33%，P＜0.05）。两组急诊PCI术后即刻cTFC均较术前显著降低（P＜0.05），且以试验组下降更显著（P＜0.05）。两组术后24 h内各项心肌酶指标（LDH、CK、CK-MB）的峰值均较术前显著升高（P＜0.05），且试验组术后 24 h 内各项心肌酶指标（LDH、CK、CK-MB）的峰值均显著低于对照组（P＜0.05）。与术前相比，两组术后24 h血清ET-1、IL-18、MMP-9、MDA水平均显著升高（P＜0.05），术后7 d以上指标则均显著降低（P＜0.05）。两组术后24 h血清NO浓度均较术前显著下降（P＜0.05），而术后7 d均较术前显著升高（P＜0.05）。且术后24 h、7 d，试验组血清ET-1、IL-18、MMP-9、MDA水平均显著低于同期对照组（P＜0.05），血清NO浓度则均显著高于同期对照组（P＜0.05）。6个月随访期间，试验组MACCE发生率（5.00%）比对照组（16.67%）显著降低（P＜0.05）。住院期间，试验组出血事件发生率（6.67%）与对照组（10.00%）比较，差异无统计学意义（P＞0.05）。结论 病灶内或冠脉内联用重组人尿激酶原与替罗非班均能改善STEMI急诊PCI患者术后心肌微循环，减轻血管内皮损伤及心肌损伤，降低机体炎症及氧化应激水平，但病灶内给药的效果更为明显。

Objective Human recombinant urokinase original and for class had combination of different dosage of ST segment elevation myocardial infarction (STEMI) emergency percutaneous coronary intervention (PCI) in patients with postoperative myocardial microcirculation, endothelial function and serum myocardial enzymes, interleukin (IL) - 18, matrix metalloproteinases 9 (MMP-9), malondialdehyde (MDA). Methods 120 STEMI patients who received emergency PCI in The Eighth People's Hospital from July 2018 to October 2021 were selected as the research objects and divided into observation group (n= 60) and control group (n=60) according to the random number table method. The observation group was treated with recombinant prourokinase and tirofiban in the lesion, while the control group was treated with recombinant prourokinase and tirofiban in the coronary artery. Thrombolysis in myocardial infarction (TIMI) blood flow grade, TIMI myocardial perfusion grade (TMPG) and corrected TIMI blood flow frame count (cTFC) were compared between the two groups before and after emergency PCI. The peak values of myocardial enzymes [creatine kinase and its isoenzyme (CK and CK-MB), cardiac troponin T (cTnT)] in the two groups were recorded within 24 hours after operation.The vascular endothelial function indexes [endothelin-1 (ET-1), nitric oxide (NO)] and serum levels of IL-18, MMP- 9 and MDA were detected before and 24 h and 7 d after emergency PCI. The incidence of major adverse cardiovascular and cerebrovascular events (MACCE) and the incidence of bleeding events in the two groups during the six-month follow-up after emergency PCI were analyzed. Results The proportion of TIMI grade three and TMPG grade three in the observation group after emergency PCI (96.67% , 95.00%) were significantly higher than those in the control group (86.67%, 83.33%, P＜0.05). The cTFC of the two groups immediately after PCI was significantly lower than that before PCI (P＜0.05), and the decrease was more significant in the observation group (P＜0.05).Within 24 h after operation, the peak values of various myocardial enzyme indexes (CK, CK-MB, cTnT) in the observation group were significantly lower than those in the control group (P＜0.05). Compared with before operation, the serum levels of ET-1, IL-18, MMP-9 and MDA in the two groups were significantly increased at 24 h after operation (P＜0.05), and the indexes above 7 d after operation were significantly decreased (P＜0.05).The serum NO concentration of the two groups at 24 h after operation was significantly decreased compared with that before operation (P＜0.05), and the serum NO concentration at 7 d after operation was significantly increased compared with that before operation (P＜0.05). At 24 h and 7 d after operation, the serum levels of ET-1, IL-18, MMP-9 and MDA in the observation group were significantly lower than those in the control group (P＜0.05), and the serum concentration of NO in the observation group was significantly higher than that in the control group (P＜0.05). During the 6-month follow-up, the incidence of MACCE in the observation group was significantly lower than that in the control group (5.00% vs 16.67%, P＜0.05). During hospitalization, the incidence of bleeding events in the observation group was 6.67% vs 10.00% in the control group, and the difference was not statistically significant (P＞0.05). Conclusions Intralesional or intracoronary administration of recombinant prourokinase and tirofiban can improve myocardial microcirculation, reduce vascular endothelial injury and myocardial injury, and reduce the level of inflammation and oxidative stress in patients with STEMI after emergency PCI, but intralesional administration is more effective.

R972

合肥职业技术学院重点项目（2023FSYYKJA01）