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This study aimed to investigate the effects of intracoronary prourokinase thrombolysis combined with emergency percutaneous coronary intervention (PCI) on myocardial perfusion and vascular endothelial function in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: A total of 104 patients with STEMI were collected from August 2020 to August 2022, and were divided into control group and observation group in a random manner. The control group received PCI directly, and the observation group received intracoronary prourokinase thrombolytic therapy before PCI. The treatment effects were evaluated by measuring the cardiac function indexes, including left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), and left ventricular ejection fraction (LVEF), the TIMI myocardial perfusion grade, the vascular endothelial indexes, including soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), the von Willebrand factor (vWF), the myocardial injury indexes, including cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), and lactate dehydrogenase (LDH), and the inflammatory factors, including myeloperoxidase (MPO), C-reactive protein (CRP), and interleukin-6 (IL-6). Furthermore, the treatment safety was assessed by recording the incidence of major MACE events, 6 months after the operation. Results: After treatment, LVEDD and LVESD were lower in the observation group than in the control group, and LVEF was higher (p < 0.05). The TIMI myocardial perfusion grade in the observation group was higher than in the control group, after treatment (p < 0.05). The levels of sICAM-1, sVCAM-1, and vWF were higher in the observation group than in the control group (p < 0.05). The levels of cTnI, CK-MB, and LDH in the observation group were lower than those in the control group, 24 hours after surgery. At 3 days after surgery, MPO was lower in the observation group than in the control group, and CRP and IL-6 were higher (p < 0.05). The incidence of major MACE events in the observation group was lower than that in the control group, 6 months after surgery (p < 0.05). There was 1 case of puncture site bleeding in the observation group, 1 case of puncture site bleeding and 1 case of subcutaneous ecchymosis in the control group, but no serious bleeding events, such as internal bleeding or cerebral hemorrhage, in the two groups. Conclusions: Intracoronary prourokinase thrombolytic therapy combined with emergency PCI can promote the recovery of cardiac function, improve myocardial perfusion and vascular endothelial function, and reduce inflammation and the incidence of major postoperative MACE events in acute STEMI patients. [ABSTRACT FROM AUTHOR]