尿激酶原对冠脉结扎大鼠心肌缺血再灌注损伤的保护作用  

Protective effect of prourokinase from myocardial ischemia reperfusion injury in coronary ligation rats

作　　者：刘江波[1] 张金盈[2] 刘志远[1] 仇瑞莉 张松雨[1] 梅艳阳[1] 赵晓宁[1] 李纲[1] LIU Jiangbo;ZHANG Jinying;LIU Zhiyuan;QIU Ruili;ZHANG Songyu;MEI Yanyang;ZHAO Xiaoning;LI Gang(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,南阳473009 [2]郑州大学第一附属医院心血管内科,郑州450052

出　　处：《西北药学杂志》2021年第1期41-46,共6页Northwest Pharmaceutical Journal

基　　金：国家自然科学基金项目(编号:81570274)。

摘　　要：目的探究尿激酶原(PRO)对冠脉结扎大鼠心肌缺血血流动力学的影响及对心肌缺血再灌注损伤(MIRI)的保护作用。方法选取60只雄性SD大鼠,体质量为200~300 g,采用随机数字表法将其均分为对照组、模型组以及PRO高、低剂量组(2,1 mg·kg^-1),每组15只;除对照组外,各组大鼠均采用冠脉结扎手术法制备MIRI模型;检测各组大鼠的平均动脉压(MAP)、左室收缩压(LVSP)和左心室舒张末压(LVEDP)水平;采用Elisa试剂盒检测血清中炎性因子白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的水平;采用试剂盒检测大鼠血清氧化应激物质超氧化物歧化酶(SOD)、活性氧(ROS)和丙二醛(MDA)水平;采用HE染色观察大鼠心肌损伤情况;采用流式细胞仪检测大鼠心肌细胞凋亡情况;采用蛋白质印迹法检测大鼠c-Jun氨基末端激酶(JNK)、磷酸化c-Jun氨基末端激酶(P-JNK)、凋亡蛋白B淋巴细胞瘤-2(Bcl-2)以及Bcl-2相关X蛋白(Bax)表达水平。结果与对照组比较,模型组大鼠MAP、LVSP、SOD和Bcl-2蛋白表达水平均显著降低;LVEDP、IL-6、IL-1β、TNF-α、MDA、ROS、心肌细胞凋亡率、Bax蛋白和P-JNK蛋白表达水平均显著升高(P<0.01),JNK蛋白表达无显著改变(P>0.05)。与模型组比较,PRO低剂量组大鼠MAP、LVSP、SOD和Bcl-2蛋白表达水平均显著升高;LVEDP、IL-6、IL-1β、TNF-α、MDA、ROS、心肌细胞凋亡率、Bax蛋白和P-JNK蛋白表达水平显著降低(P<0.01),JNK蛋白表达无显著改变(P>0.05)。与PRO低剂量组比较,PRO高剂量组大鼠MAP、LVSP、SOD和Bcl-2蛋白表达水平均显著升高,LVEDP、IL-6、IL-1β、TNF-α、MDA、ROS、心肌细胞凋亡率、Bax蛋白和P-JNK蛋白表达水平显著降低(P<0.01),JNK蛋白表达无显著改变(P>0.05)。结论PRO可改善冠脉结扎大鼠心肌缺血的血流动力学,并通过抑制JNK信号通路的活化从而抑制MIRI大鼠的炎症反应及氧化应激反应。Objective To explore the effects of prourokinase(PRO)on hemodynamics of myocardial ischemia and myocardial ischemia-reperfusion injury(MIRI)in coronary ligation rats.Methods 60 male SD rats weighing 200-300 g were enrolled.They were divided into control group,model group,PRO high and low dose groups(2 and 1 mg·kg^-1)by random number table method,15 cases in each group.Except for control group,MIRI models were prepared by coronary ligation in other groups.The levels of mean artery pressure(MAP),left ventricular systolic pressure(LVSP)and left ventricular end-diastolic pressure(LVEDP)levels in each group were detected.Elisa kit was applied to detect levels of serum inflammatory factors such as interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α).The levels of serum oxidative stress substances such as superoxide dismutase(SOD),reactive oxygen species(ROS)and malondialdehyde(MDA)were detected by kits.The myocardial injury situations were observed by HE staining.The apoptosis of myocardial cells was detected by flow cytometry.The expression of c-Jun N-terminal kinase(JNK),phosphorylated JNK(P-JNK)and apoptosis proteins[B-cell lymphoma-2(Bcl-2),Bcl-2 associated X protein(Bax)]was detected by Western Blot.Results Compared with control group,MAP,LVSP,SOD and Bcl-2 protein levels were significantly decreased in model group,while LVEDP,IL-6,IL-1β,TNF-α,MDA,ROS,apoptosis rate of cardiomyocyte,relative expression levels of Bax and P-JNK proteins were significantly increased(P<0.01),and there was no significant change in expression of JNK protein(P>0.05).Compared with model group,MAP,LVSP,SOD and Bcl-2 protein levels were significantly increased in PRO low dose group,while LVEDP,IL-6,IL-1β,TNF-α,MDA,ROS,apoptosis rate of cardiomyocyte,relative expression levels of Bax and P-JNK proteins were significantly decreased(P<0.01),and there was no significant change in expression of JNK protein(P>0.05).Compared with PRO low dose group,MAP,LVSP,SOD and Bcl-2 protein levels were significantly increased i

关 键 词：尿激酶原 心肌缺血 冠脉结扎 缺血再灌注损伤 

分 类 号：R965[医药卫生—药理学]