携IL-6单克隆抗体靶向微泡破坏技术在兔MI/RI损伤中的应用  

Application of Ultrasound-Targeted Microbubble Destruction with IL-6 Monoclonal Antibody in Rabbit Myocardial Ischemia-Reperfusion Injury

作　　者：杨媛 梁红敏[2] 朱桂敏 杨寒凝 曹维涵 陆永萍 YANG Yuan;LIANG Hong-min;ZHU Gui-min;YANG Han-ning;CAO Wei-han;LU Yong-ping(Dept.of Medical Ultrasound,The Fourth Affiliated Hospital of Kunming Medical University,The Second Hospital of Yunnan Province,Kunming Yunnan 650021;Dept.of Medical Ultrasound,The First Affiliated Hospital of Kunming Medical University,Kunming Yunnan 650032,China)

机构地区：[1]昆明医科大学第四附属医院,云南省第二人民医院超声科,云南昆明650021 [2]昆明医科大学第一附属医院超声科,云南昆明650021

出　　处：《昆明医科大学学报》2021年第2期6-12,共7页Journal of Kunming Medical University

基　　金：国家自然科学基金资助项目(81660084);云南省医学领军人才培养基金资助项目(L-201616);云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目[2017FE467(-091)]。

摘　　要：目的探讨携IL-6单克隆抗体超声靶向微泡破坏技术(ultrasound-targeted microbubble destruction,UTMD)联合不同超声辐照强度在心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MI/RI)中的应用价值。方法将大耳兔90只随机分为3组:A组(15只)关胸对照组、B组(15只)开胸对照组、C组(60只)缺血/再灌注组,其中C组又根据再灌注时间(30 min、60 min、120 min、180 min)分成T1、T2、T3、T4时段,各组再分为U_(0)组(未经超声辐照)、U_(1)组(0.5 w/cm^(2)强度)、U_(2)组(0.75 w/cm^(2)强度)。将冠状动脉左前降支阻断30 min,解除阻断后得到MI/RI损伤模型,经耳缘静脉注射携IL-6单抗靶向造影剂,随后进行超声辐照。应用QLAB10.5软件分析辐照前、后再灌注损伤区心肌的视频强度,得到视频强度差值(video intensity difference,VID)。ELISA检测辐照前、后心肌组织中IL-6含量。结果T1-T4时段U_(2)组VID值较U_(1)组高(P<0.05),各时段U_(2)组和U_(1)组VID值两两比较,差异无统计学意义(P>0.05)。ELISA结果显示:超声辐照后,T1-T4时段,U_(2)组IL-6含量比U_(1)组低(P<0.05);VID值和心肌组织内IL-6水平差值呈正相(rU_(1)=0.745,rU_(2)=0.734,P<0.05);HE染色显示,U_(2)组与U_(1)组比较,炎性细胞浸润减少,心肌细胞损伤减轻。结论携IL-6单克隆抗体靶向微泡破坏技术联合超声辐照能有效缓解MI/RI的炎症反应,且在不损伤心肌的前提下,干预越早,辐照强度越强,减轻炎症反应的效果越佳。Objective To explore the application value of Ultrasound Targeted Microbubble Destruction(UTMD)with IL-6 monoclonal antibody combined with different ultrasonic irradiation intensity in myocardial ischemia-reperfusion injury(MI/RI).Methods Ninety rabbits were randomly divided into 3 groups,including 15 rabbits in the thoracotomy control group(group A),15 rabbits in the thoracotomy control group(group B),and 60 rabbits in the R/I group(group C,divided into T1-T4 periods,reperfusion for 30 min,60 min,120 min,and 180 min).Each group was further divided into group U_(0)(without ultrasonic irradiation),group U_(1)(0.5 w/cm^(2) intensity),group U_(2)(0.75 w/cm^(2) intensity).An animal model of MI/RI was obtained by blocking the left anterior descending branch of the coronary artery for 30 min and then releasing it from reperfusion.The targeted contrast agent containing IL-6 was injected through ear vein,and then ultrasound irradiation was performed.QLAB10.5 software to analyze the video intensity of myocardium in reperfusion injury area before and after irradiation,and the ultrasonic video intensity difference(VID)was calculated.The content of IL-6 in the myocardium of each group before and after irradiation was detected by ELISA.Results The VID value of U_(2) group was higher than that of U_(1) group during T1-T4(P<0.05).The values of U_(2) and U_(1) VID in theT1-T4 period were compared in pairs within the group,the difference was not statistically significant(P>0.05).ELISA analysis of rabbit myocardial tissue showed that the content of IL-6 in U_(2) group was lower than that in U_(1) group during T1-T4 period after ultrasonic irradiation(P<0.05).The difference of IL-6 content between U_(1) group and U_(2)group during T1-T4 was compared in pairs within the group,the difference was not statistically significant(P>0.05).The difference of IL-6 content in myocardial tissue was positively correlated with the mean difference of ultrasonic video intensity(rU_(1)=0.745,rU_(2)=0.734).Conclusion IL-6 monoclonal antibody microbub

关 键 词：心肌缺血再灌注损伤 心肌声学造影 超声靶向微泡破坏技术 IL-6单克隆抗体 

分 类 号：R445.1[医药卫生—影像医学与核医学]