超声微泡靶向介导MaFGF对阿霉素心肌病防治作用的初步实验研究  

Prevention of doxorubicin induced cardiomyopathy after delivery of modified acidic fibroblast growth factor by using ultrasound-targeted microbubble destruction： a preliminary experimental study

作　　者：倪贤伟 田新桥[2] 赵应征[3] 郑磊[4] 李剑敏[5] 吕夕明[1] 何慧疗[1] 毛凯丽 田福荣 郑靖宇 

机构地区：[1]温州医科大学附属第二医院超声科,325027 [2]河南省人民医院超声科 [3]温州医科大学 [4]温州医科大学附属第一医院超声科 [5]温州医科大学附属第一医院病理科

出　　处：《中华超声影像学杂志》2017年第1期71-76,共6页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金（81571696,81301982）;温州市公益性科技计划项目（Y20140726）

摘　　要：目的探讨应用超声靶向微泡击破技术（ultrasound—targetedmicrobubbledestruction，UTMD）介导改构型酸性成纤维细胞生长因子（modifiedacidicfibroblastgrowthfactor，MaFGF）对大鼠阿霉素心肌病（doxorubiciwinducedcardiomyopathy，DOX—CM）的防治作用。方法5（）只健康雄性SD大鼠随机平分为5组：①正常对照组；②DOX—CM模型组；③单纯MaFGF组；④UTMD组；⑤MaFGF＋UTMD组。②～⑤组大鼠经腹腔注射盐酸阿霉素（DOX）并给予对应干预。干预6周后对所有大鼠行常规超声心动图及速度向量成像（VVI）检查，测定左室舒张末期内径（LVIDd）、左室收缩末期内径（LvIDs）、左室射血分数（LVEF）、左室短轴缩短率（LVFs）、乳头肌水平左室壁各节段平均径向峰值速度（Vs）、径向应变（Sr）及径向应变率（SRr）。测量结束后处死大鼠取心肌组织，HE染色观察其组织形态学变化，苦味酸天狼猩红（VG）染色计算心肌胶原容积分数（CVF）。结果干预6周后，MaFGF＋UTMD组心脏／体重比值（HW／BW）、LVIDs及LVIDd较DOXCM模型组明显下降（均P〈0．（15），LVEF、LVFS、Vs、Sc及Sr明显增高（均P〈0．05）；VG染色显示与正常对照组相比DOX—CM模型组胶原容积分数（CVF）明显增高（P〈0．01），而MaFGF＋UTMD组CVF降低（P〈0．01）。结论应用UTMD介导MaFGF可减缓DOX—CM大鼠心肌纤维化形成，有效保护D0x_CM大鼠的左心室收缩功能。Objective To observe the preventive effects of doxorubicin-induced cardiomyopathy （DOX-CM） rats after delivery of modified acidic fibroblast growth factor （MaFGF） by using ultrasound targeted microbubble destruction （UTMD）. Methods Fifty male SD rats were randomly divided into five groups ： Control group ; C）DOX-CM group ; MaFGF group; UTMD group; 0 MaFGF ＋ UTMD group. groups were intraperitoneally injected with doxorubicin to induce DOX-CM and given the corresponding interventions. Six weeks after intervention, all rats were underwent conventional echocardiography and velocity vector imaging （VVI） exams. Left ventricular internal dimension-diastole （ LVIDd）, left ventricular internal dimension-systole （ LVIDs）, left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （LVFS） were measured using conventional echocardiography. The segmental mean peak systolic radial velocity （Vs）, systolic radial strain （Sr）, and systolic radial strain rate （SRr） of six wails at the papillary muscle level were measured in left ventricular short axis view by VVI. At last, myocardial tissues of all rats were stained with HE to observe the myocardial tissue morphology and with Van Gieson （VG） to calculate the collagen volume fractions （CVF）. Results Six weeks after intervention,heart weight/body weight （HW/BW）, LVIDs and LVIDd of MaFGF ＋ UTMD＋rouD weresignificantly decreased compared with those of DOX-CM group（ P〈0.05）, while the LVEF, LVFS, Vs, Sc and Sr were significantly increased （ P 〈 0.05）. Van Gieson stains showed that the collagen volume fractions （CVF） of DOX-CM groups significantly increased compared with that of the control group （ P〈0.01 ）, while the CVF of MaFGF ＋ UTMD groups significantly decreased （ P〈0.01 ）. Conclusions Delivery of MaFGF to myocardium in DOX-CM rats by UTMD could retard the formation of myocardial fibrosis and effectively protect the left ventricular function of DOX-CM rats.

关 键 词：超声心动描记术 微气泡 酸性成纤维细胞生长因子 心肌病 阿霉素 

分 类 号：R540.45[医药卫生—心血管疾病] R542.2[医药卫生—内科学]