纳米脂质体结合微泡靶向介导改构型酸性成纤维细胞生长因子对糖尿病大鼠左心室收缩功能的影响  

Effects of modified acidic fibroblast growth factor mediated by nanoliposomes combined with ultrasound-targeted microbubble destruction on left ventricular systolic function in diabetic rats

作　　者：郑磊 沈传利 赵应征 倪贤伟 李剑敏[5] 颜宁 田新桥 Zheng Lei;Shen Chuanli;Zhao Yingzheng;Ni Xianwei;Li Jianmin;Yan Ning;Tian Xinqiao(Department of Ultrasonography,Zhengzhou University People′s Hospital(Henan Provincial People′s Hospital),Central China Fuwai Hospital,Zhengzhou 450003,China;Department of Ultrasonography,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325027,China;School of Pharmaceutical Sciences,Wenzhou Medical University,Wenzhou 325035,China;Department of Ultrasonography,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;Department of Pathology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325027,China)

机构地区：[1]郑州大学人民医院(河南省人民医院)华中阜外医院超声科,450003 [2]温州医科大学附属第一医院超声科,325027 [3]温州医科大学药学院,325035 [4]温州医科大学附属第二医院超声科,325000 [5]温州医科大学附属第一医院病理科,325027

出　　处：《中华超声影像学杂志》2020年第1期70-76,共7页Chinese Journal of Ultrasonography

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

摘　　要：目的探讨应用纳米脂质体结合超声靶向微泡爆破(UTMD)技术介导改构型酸性成纤维细胞生长因子(MaFGF)对糖尿病(DM)早期大鼠左心室收缩功能的影响。方法采用逆相蒸发法制备包载MaFGF的纳米脂质体。60只健康雄性SD大鼠随机挑选50只经腹腔注射链脲佐菌素(STZ)建立DM模型,其余10只作为对照组。将DM大鼠随机分为DM模型组、单纯MaFGF溶液组、MaFGF纳米脂质体组及MaFGF纳米脂质体+UTMD组。DM模型诱导成功后每周干预两次,共计12周。各组于干预结束后行常规超声心动图及速度向量成像(VVI)检查,常规超声心动图测量左室射血分数(LVEF)、左心室短轴缩短率(LVFS),VVI测定乳头肌水平左室短轴观各节段平均峰值速度(Vs)、径向应变(Sr)及径向应变率(SRr)。处死大鼠,取心脏组织,用天狼星红染色法和TUNEL染色测定各组大鼠心肌胶原容积分数(CVF)和心肌细胞凋亡指数(AI),并通过透射电子显微镜观察心肌超微结构的变化。结果本研究所制备的MaFGF纳米脂质体形态较圆整,分散均匀、稳定性好且包封率高。干预12周后,DM模型组LVEF、LVFS、Vs、Sr及SRr较对照组明显降低(均P<0.05),而MaFGF纳米脂质体+UTMD组LVEF、LVFS、Vs、Sr及SRr较DM模型组及其他各干预组明显升高(均P<0.05)。天狼星红染色及TUNEL染色结果显示,DM模型组CVF、AI明显高于对照组(均P<0.05);MaFGF纳米脂质体+UTMD组CVF、AI较DM模型组及其他各干预组显著减低(均P<0.05)。透射电镜结果显示,与DM模型组相比,MaFGF纳米脂质体+UTMD组心肌超微结构改善最为明显。结论应用纳米脂质体结合微泡靶向技术介导MaFGF可有效改善DM大鼠左心室收缩功能,其机制主要是MaFGF通过抑制心肌间质纤维化和减少心肌细胞的凋亡,从而实现心脏的保护作用。Objective To investigate the effects of modified acidic fibroblast growth factor(MaFGF)mediated by nanoliposomes combined with ultrasound-targeted microbubble destruction(UTMD)on left ventricular systolic function in early diabetes mellitus(DM)rats.Methods The nanoliposomes containing MaFGF(MaFGF-nlip)were prepared by reverse phase evaporation method.Among 60 male Sprague Dawley(SD)rats,50 rats were randomly selected and were induced to be DM models by streptozotocin(STZ)through intraperitoneal injecting,the other 10 rats as control group.Then DM rats were randomly divided into 4 groups:DM model group,MaFGF solution group,MaFGF-nlip group and MaFGF-nlip+UTMD group.After the successful induction of DM model,the intervention was performed twice a week.After 12 weeks of intervention,all rats underwent conventional echocardiography and velocity vector imaging(VVI).Left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)were measured by conventional echocardiography.The mean peak systolic radial velocity(Vs),radial strain(Sr)and 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 tissue of all rats were stained with Sirius red to evaluate myocardial interstitial fibrosis.The level of myocardial apoptosis was evaluated by TUNEL staining,and the changes of myocardial ultrastructure were observed by transmission electron microscopy.Results The prepared MaFGF-nlip were more rounded,evenly dispersed,and of good stability and high encapsulation efficiency.Twelve weeks later after intervention,LVEF,LVFS,Vs,Sr and SRr in the DM model group were significantly lower than those in the control group(all P<0.05).LVEF,LVFS,Vs,Sr and SRr in the MaFGF-nlip+UTMD group were significantly higher than those of the DM model group and other intervention groups(all P<0.05).The results of Sirius red staining and Tunel staining showed that CVF and AI in the DM model group were significantly higher than those in the control g

关 键 词：超声靶向微泡爆破技术 糖尿病心肌病 心室功能 左 纳米脂质体 改构型酸性成纤维细胞生长因子 

分 类 号：R54[医药卫生—心血管疾病] R587[医药卫生—内科学]