目的 探討尿激酶原（Pro-UK）對(duì)心肌缺血再灌注（MI/R）損傷大鼠心功能及血清心肌酶活性的影響及其機(jī)制。方法 將大鼠隨機(jī)分為假手術(shù)組、MI/R模型組和Pro-UK低、中、高劑量（0.5、1.0、2.0 mg/kg）組，Pro-UK低、中、高劑量（0.5、1.0、2.0 mg/kg）組大鼠分別于造模前給藥，前3 d每天尾iv 0.5、1.0、2.0 mg/kg Pro-UK，后2 d每天尾iv給予0.25 mg/kg Pro-UK，假手術(shù)組、模型組尾iv給予等量生理鹽水，預(yù)處理完成后均采用手術(shù)結(jié)扎的方式復(fù)制大鼠MI/R模型，其中假手術(shù)組不進(jìn)行結(jié)扎操作，再灌注150 min后測(cè)量心率，摘眼球取血后處死大鼠，取左心室，伊文思藍(lán)-TTC法檢測(cè)心肌梗死面積，HE染色觀(guān)察心肌組織病理情況，TUNEL法檢測(cè)心肌細(xì)胞凋亡情況，試劑盒檢測(cè)血清肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、乳酸脫氫酶（LDH）、纖溶酶原激活劑抑制劑1（PAI-1）和組織纖維溶酶原激活物（t-PA）水平，Western blotting檢測(cè)心肌組織中線(xiàn)粒體凋亡關(guān)鍵蛋白以及核因子κB（NF-κB）-p65蛋白磷酸化水平。結(jié)果 Pro-UK預(yù)處理能夠明顯降低MI/R大鼠心肌梗死面積、CK、CK-MB、LDH、PAI-1水平、升高t-PA水平，加快心率，能夠改善心肌病理?yè)p傷，降低心肌細(xì)胞凋亡率，同時(shí)抑制Caspase-3、p-p65、Bax蛋白表達(dá)，促進(jìn)Bcl-2蛋白表達(dá)。結(jié)論 Pro-UK預(yù)處理能夠改善MI/R損傷大鼠心功能并抑制血清心肌酶活性，其作用機(jī)制可能與NF-κB信號(hào)有關(guān)。

Objective To explore the effects and mechanism of prourokinase (Pro-UK) on cardiac function and activities of serum myocardial enzymes in rats with myocardial ischemia-reperfusion (MI/R) injury. Methods Rats were randomly divided into sham operation (Sham) group, MI/R model group, L-Pro-UK group, M-Pro-UK group and H-Pro-UK group (0.5, 1.0 and 2.0 mg/kg). In L-Pro-UK group, M-Pro-UK group and H-Pro-UK group, rats were injected with 0.5, 1.0 and 2.0 mg/kg Pro-UK in the tail vein at 3 d before modeling, respectively. And then they were continuously given 0.25 mg/kg Pro-UK injection. Sham group and MI/R model group were given the same amount of normal saline. After pretreatment, MI/R model rats were replicated by surgical ligation. Rats in the Sham group was not given ligation. After 150 minutes of reperfusion, heart rate (HR) was measured. After eyeball enucleation and blood collecting, the rats were sacrificed to obtain left ventricles. The areas of myocardial infarction were detected by Evans blue-TTC. The pathology situations of myocardial tissues were observed by HE staining. The apoptosis of myocardial cells were detected by TUNEL. The levels of serum myocardial enzymes creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) were detected by kits. The phosphorylation levels of mitochondrial apoptosis protein and nuclear factor kappa B (NF-κB)-p65 protein in myocardial tissues were detected by Western blotting. Results Pro-UK pretreatment could significantly reduce myocardial infarction area of MI/R, and reduce CK, CK-MB, LDH, PAI-1 and t-PA levels, accelerate HR, improve myocardial pathological damage, reduce apoptosis rate of myocardial cells, inhibit the expression of Caspase-3, p-p65 and Bax, and promote the expression of Bcl-2. Conclusion Pro-UK pretreatment can improve cardiac function and inhibit serum myocardial enzymes in rats with MI/R injury. The mechanism may be related to NF-κB signaling.

R286.2

國(guó)家自然科學(xué)基金資助項(xiàng)目（81570274）；鄭州大學(xué)第一附屬醫(yī)院跨學(xué)科協(xié)同攻關(guān)博士科研團(tuán)隊(duì)基金資助項(xiàng)目（2016-BSTDJJ-19）