超声微泡介导MaFGF对阿霉素心力衰竭大鼠心功能的保护作用及其机制研究  

Protective effects of Ma FGF mediated by ultrasound microbubbles on rats with heart failure induced by adriamycin and its mechanism: a preliminary experimental study

作　　者：倪贤伟 田新桥 赵应征[3] 郑磊[4] 李剑敏[5] NI Xianwei;TIAN Xinqiao;ZHAO Yingzheng(Department of Ultrasonography,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325027,China)

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(郑州大学人民医院)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：《心电与循环》2019年第6期458-462,I0001,共6页Journal of Electrocardiology and Circulation

基　　金：国家自然科学基金项目(81571696);温州市公益性科技计划项目(Y20180186、Y20170049)

摘　　要：目的观察超声靶向微泡击破(UTMD)技术调控改构型酸性成纤维细胞生长因子(MaFGF)对阿霉素心力衰竭(HF)大鼠心功能的保护作用并探讨其机制。方法随机将40只实验动物(雄性健康SD大鼠)分为正常对照组、HF模型组、MaFGF组和MaFGF+UTMD组。后3组大鼠通过腹腔注入盐酸阿霉素,MaFGF+UTMD组大鼠经尾静脉注射内含MaFGF的超声微泡混悬液后心脏接受超声靶向微泡击破处理。经过6周干预,超声心动图检查测量左心室收缩末期内径(LVESd)、左心室舒张末期内径(LVEDd)、左心室短轴缩短率(LVFS)以及左心室射血分数(LVEF)。其后处死大鼠取心肌组织,检测心肌丙二醛(MDA)、超氧化物歧化酶(SOD)水平,通过Masson胶原染色计算心肌胶原容积分数(CVF)、血管周围胶原面积(PVCA)/血管腔面积(LA)比值,透射电镜下对心肌细胞超微结构进行观察。结果经过干预6周后,MaFGF+UTMD组LVESd及LVEDd较HF模型组减小(均P<0.05),LVEF、LVFS增高(均P<0.05);HF模型组心肌MDA较正常对照组升高,而SOD降低(均P<0.05),经过MaFGF+UTMD干预,MaFGF+UTMD组SOD上升而MDA降低(均P<0.05);Masson胶原染色显示与正常对照组比较HF模型组CVF与PVCA/LA增高(均P<0.05),而MaFGF+UTMD组这两项指标则下降(均P<0.05);透射电镜显示HF大鼠心脏结构明显异常且能量代谢紊乱,而由UTMD介导的MaFGF干预后,大鼠的心脏微观形态有所改善。结论对于由阿霉素诱导的心肌损伤,UTMD介导MaFGF对左心室收缩机能具有保护性,其机制可能与MaFGF缓解ROS损害心肌线粒体膜程度,抑制心肌纤维化的形成有关。Objective To observe the protective effect and possible mechanisms of modified acidic fibroblast growth factor(Ma FGF)mediated by ultrasound-targeted microbubble destruction(UTMD)on cardiac function in adria-mycin-induced heart failure(HF)rats.Methods Forty male SD rats were randomly assigned to control group,HF group,Ma FGF group and Ma FGF+UTMD group.The later 3 groups were injected with adriamycin(ADR)intraperitoneally.The heart treated by UTMD after injected with ultrasound microbubble suspension containing Ma FGF via tail vein in Ma FGF+UTMD group.Echocardiography was performed to measure left ventricular(LV)end systolic dimension(LVESd),LV end diastolic dimension(LVEDd),LV short axis shortening rate(LVFS)and LV ejection fraction(LVEF)after 6 weeks of intervention.Then the rats were sacrificed to measure myocardial SOD and MDA content.Myocardial collagen volume fraction(CVF)and the ratio of the perivascular collagen area to the luminal area(PVCA/LA)were calculated by Masson staining.The ultrastructural changes of cardiomyocyte were observed under transmission electron microscope(TEM).Results After 6 weeks of intervention,LVESd and LVEDd significantly reduced,LVEF and LVFS significantly increased in Ma FGF+UTMD group compared with HF group(all P<0.05).Myocardial MDA increased while SOD decreased significantly(all P<0.05)in HF group compared with control group.After Ma FGF+UTMD intervention,myocardial SOD increased significantly and MDA decreased significantly(all P<0.05).Masson collagen staining showed CVF and PVCA/LA increased significantly in HF group and decreased significantly in Ma FGF+UTMD group compared with control group(all P<0.05).TEM showed significant abnormal of cardiac structure and energy metabolic in HF group.After receiving the intervention of Ma FGF mediated by UTMD,myocardial ultrastructure was significantly improved.Conclusion Ma FGF mediated by UTMD can improve LV systolic function in rats with myocardial injury induced by ADR via alleviating ROS damage to myocardial mitochondrial membran

关 键 词：酸性成纤维细胞生长因子 微泡 超声靶向微泡爆破技术 心力衰竭 

分 类 号：R54[医药卫生—心血管疾病]