摘要目的 探讨应用超声靶向微泡击破技术(ultrasound-targeted microbubble destruction,UTMD)介导改构型酸性成纤维细胞生长因子(modified acidic fibroblast growth factor,MaFGF)对大鼠阿霉素心肌病(doxorubicin-induced cardiomyopathy,DOX-CM)的防治作用.方法 50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DOX-CM模型组明显下降(均P<0.05),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DOX-CM大鼠的左心室收缩功能.

abstractsObjective 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:①Control group;②DOX-CM group;③MaFGF group;④UTMD group;⑤MaFGF+UTMD group.② ~ ⑤ 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 walls 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 group were significantly 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.