尿激酶原对心肌缺血再灌注损伤大鼠心功能及血清心肌酶活性的影响  

Effects of prourokinase on cardiac function and activities of serum myocardial enzymes in rats with myocardial ischemia-reperfusion injury

作　　者：赵晓宁[1] 刘志远[1] 刘江波[1] 李纲[1] 张金盈[2] ZHAO Xiao-ning;LIU Zhi-yuan;LIU Jiang-bo;LI Gang;ZHANG Jin-ying(Department of Cardiovascular Medicine,Nanyang Central Hospital,Nanyang 473009,China;Department of Cardiovascular Medicine,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]南阳市中心医院心血管内科,河南南阳473009 [2]郑州大学第一附属医院心血管内科,河南郑州450052

出　　处：《现代药物与临床》2020年第10期1937-1942,共6页Drugs & Clinic

基　　金：国家自然科学基金资助项目(81570274);郑州大学第一附属医院跨学科协同攻关博士科研团队基金资助项目(2016-BSTDJJ-19)。

摘　　要：目的探讨尿激酶原(Pro-UK)对心肌缺血再灌注(MI/R)损伤大鼠心功能及血清心肌酶活性的影响及其机制。方法将大鼠随机分为假手术组、MI/R模型组和Pro-UK低、中、高剂量(0.5、1.0、2.0mg/kg)组,Pro-UK低、中、高剂量(0.5、1.0、2.0 mg/kg)组大鼠分别于造模前给药,前3 d每天尾iv 0.5、1.0、2.0 mg/kg Pro-UK,后2 d每天尾iv给予0.25 mg/kg Pro-UK,假手术组、模型组尾iv给予等量生理盐水,预处理完成后均采用手术结扎的方式复制大鼠MI/R模型,其中假手术组不进行结扎操作,再灌注150min后测量心率,摘眼球取血后处死大鼠,取左心室,伊文思蓝-TTC法检测心肌梗死面积,HE染色观察心肌组织病理情况,TUNEL法检测心肌细胞凋亡情况,试剂盒检测血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、纤溶酶原激活剂抑制剂1(PAI-1)和组织纤维溶酶原激活物(t-PA)水平,Western blotting检测心肌组织中线粒体凋亡关键蛋白以及核因子κB(NF-κB)-p65蛋白磷酸化水平。结果Pro-UK预处理能够明显降低MI/R大鼠心肌梗死面积、CK、CK-MB、LDH、PAI-1水平、升高t-PA水平,加快心率,能够改善心肌病理损伤,降低心肌细胞凋亡率,同时抑制Caspase-3、p-p65、Bax蛋白表达,促进Bcl-2蛋白表达。结论Pro-UK预处理能够改善MI/R损伤大鼠心功能并抑制血清心肌酶活性,其作用机制可能与NF-κB信号有关。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.

关 键 词：尿激酶原 心肌缺血再灌注 心肌酶 肌酸激酶 肌酸激酶同工酶 乳酸脱氢酶 核因子-κB 纤溶酶原激活剂抑制剂1 组织纤维溶酶原激活物 

分 类 号：R286.2[医药卫生—中药学]