左西孟旦对猪冠状动脉微栓塞后心肌细胞炎症反应的影响  

Levosimendan pretreatment inhibits myocardial inflammation in swine after coronary microembolization

作　　者：王江友[1] 陈涵[1] 宋丹[1] 刘成伟[1] 彭剑[1] 苏晞[1] 鄢华[1] 张龙岩 WANG Jiang-you;CHEN Han;SONG Dan;LIU Cheng-wei;PENG Jian;SU Xi;YAN Hua;ZHANG Long-yan(Department of Cardiology,Wuhan Asia Heart Hospital,Wuhan 430000,China)

机构地区：[1]武汉亚洲心脏病医院心内科,湖北武汉430022

出　　处：《中国介入心脏病学杂志》2018年第10期584-588,共5页Chinese Journal of Interventional Cardiology

基　　金：武汉市卫生计生科研基金资助(WX17Q36);湖北省卫生计生科研基金资助(WJ2018H0108);中国中青年临床研究基金-VG基金(2017-CCA-VG-001)

摘　　要：目的探讨左西孟旦对猪急性冠状动脉微栓塞(CME)后心肌细胞炎症反应的影响及意义。方法将健康巴马系小型猪随机分为CME+左西孟旦组、假手术组及CME组,每组5只。采用经皮冠状动脉介入治疗法,于左前降支中段(发出第一对角支)处,经微导管在40 min内注入42μm的微栓塞球45 ml(假手术组注射等量生理盐水),再用10 ml生理盐水冲洗微导管并注入冠状动脉内。CME+左西孟旦组在CME建立前以左西孟旦预处理[从耳缘静脉以0.05μg/(kg·min)使用24 h,术前60 min再以0.2μg/(kg·min)负荷使用]。术后12 h采用超声心动图检测心功能包括左心室舒张末期内径(LVEDd)、左心室射血分数(LVEF)、心排血量(CO)及左心室短轴缩短率(FS),以Western blot检测活化肿瘤坏死因子α(TNF-α)表达水平。结果 CME组术后12 h FS[(24.49±2.86)%比(41.28±2.86)%,P=0.023]、LVEF[(49.83±4.64)%比(66.86±3.97)%,P=0.035]、CO[(2.58±0.42) L/min比(4.32±0.89) L/min,P=0.042]与假手术组比较均显著下降,而LVEDd[(38.26±1.93) mm比(32.39±1.52) mm,P=0.043]比假手术组显著增加,差异均具有统计学意义。CME+左西孟旦组FS[(32.42±3.98)%比(24.49±2.86)%,P=0.029]、LVEF[(58.42±5.28)%比(49.83±4.64)%,P=0.043]、CO[(3.58±0.92) L/min比(2.58±0.42)L/min,P=0.038]与CME组比较均呈现升高趋势,LVEDd [(33.92±1.56)mm比(38.26±1.93) mm,P=0.037]比CME组呈现降低趋势,差异均有统计学意义。Western blot定量分析显示,CME组与对照组比较,心肌组织TNF-α蛋白表达水平较高(P=0.039);CME+左西孟旦组与CME组比较,心肌组织TNF-α蛋白表达水平较低(P=0.042),差异均有统计学意义。结论左西孟旦预处理可明显减少CME后心肌细胞炎症反应并改善心功能,其机制可能是通过抑制心肌细胞促炎蛋白TNF-α表达来实现。Objective Aim To explore the eff ect of levosimendan on myocardial infl ammation after coronary microembolization(CME)in swine models.Methods Fifteen swine models were randomly and equally assigned into sham-operated(control)group,CME group and levosimendan group.CME was induced by injection of microspheres selectively into left anterior descending artery in the CMEgroup,while the same dose of normal saline was substituted for microspheres in the control group.Swines in the levosimendan group were pretreated with injection of levosimendan through vein at 0.05μg/(kg·min)for 24 hours,and a bolus of 0.2μg/(kg·min)at 60 minutes before microspheres injection.Cardiac function was assessed by echocardiography and the expression level of TNF-αwas measured by Western blot 12 hours after operation.Results Compared with the sham-operated group,cardiac function was signifi cantly reduced in the CME group(P<0.05).Cardiac function was signifi cantly improved in the levosimendan group comparing with the CME group(P<0.05).Compared with the control group,myocardial inflammation and the levels of TNF-αincreased significantly in the CME group(P<0.05).These changes were ameliorated by application of levosimendan(P<0.05).Conclusions Pretreatment with levosimendan can reduce myocardial inflammation and improve cardiac function after CME.The mechanism may be due to inhibition of the expression of pro-infl ammation protein TNF-αin cardiomyocytes.The data generated from this study provide a rationale for the development of myocardial infl ammation-based therapeutic strategies for CME-induced myocardial injury.

关 键 词：左西孟旦 冠状动脉 微栓塞 炎症反应 

分 类 号：R541.4[医药卫生—心血管疾病]