MaFGF纳米脂质体结合超声靶向微泡爆破对阿霉素心肌病大鼠心肌细胞凋亡的影响  

Effect of MaFGF Nanoliposome Combined with Ultrasound Targeted Microbubble Destruction Technology on Cardiomyocyte Apoptosis in Rats with Doxorubicin Cardiomyopathy

作　　者：倪贤伟 赵应征 余方芳 王小花 田新桥 NI Xianwei;ZHAO Yingzheng;YU Fangfang(The Second Affiliated Hospital of Wenzhou Medical University and Yuying Children′s Hospital,Zhejiang 325027,China)

机构地区：[1]温州医科大学附属第二医院、育英儿童医院超声科,325027 [2]温州医科大学药学院,325035 [3]河南省阜外华中心血管医院超声科,郑州451460

出　　处：《医学研究杂志》2022年第3期99-103,共5页Journal of Medical Research

基　　金：浙江省温州市公益性科技计划项目(Y20180186)。

摘　　要：目的探讨改构型酸性成纤维细胞生长因子(MaFGF)纳米脂质体(NP)结合超声靶向微泡爆破技术(UTMD)对阿霉素心肌病(DOX-CM)大鼠心肌细胞凋亡的影响及机制。方法随机将50只健康雄性SD大鼠分为:正常对照组、DOX-CM模型组、MaFGF溶液组、MaFGF-NP组及MaFGF-NP+UTMD组(n=10)。干预6周后,应用超声心动图测定所有大鼠的左心室舒张末期内径(LVIDd)、左心室收缩末期内径(LVIDs)、左心室射血分数(LVEF)和左心室短轴缩短率(LVFS)。实验结束后,取大鼠心肌组织,通过TUNEL荧光染色法观察心肌细胞凋亡情况,蛋白免疫印迹法测定心肌凋亡相关蛋白表达。结果与DOX-CM模型组比较,MaFGF-NP+UTMD组LVIDs及LVIDd明显减小,LVEF、LVFS明显增高,而TUNEL染色结果显示,MaFGF-NP+UTMD组大鼠心肌细胞凋亡明显减少;蛋白免疫印迹法检查结果显示,MaFGF-NP+UTMD组较DOX-CM模型组pAKT/AKT比值和BAX的含量减低,BCL-2的含量升高。结论MaFGF-NP结合UTMD可减轻阿霉素所致心肌损伤,其机制可能与MaFGF减少阿霉素引起的心肌细胞凋亡有关。Objective To explore the effect and mechanism of modified acidic fibroblast growth factor(MaFGF)nanoliposomes(NP)combined with ultrasound targeted microbubble destruction technology(UTMD)on cardiomyocyte apoptosis in rats with doxorubicin cardiomyopathy.Methods Fifty healthy male SD rats were randomly divided into 5 groups:control group,doxorubicin cardiomyopathy(DOX-CM)group,MaFGF solution group,MaFGF-NP group and MaFGF-NP+UTMD group.After 6 weeks of intervention,all rats were subjected to echocardiography to determine the left ventricular internal dimension-diastole(LVIDd)and left ventricular internal dimension-systole(LVIDs),left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS).After the measurement,the rats were sacrificed and myocardial tissue was taken,and the apoptosis of myocardial cells was observed by TUNEL fluorescent staining,the expression of myocardial apoptosis-related proteins was determined by Western blotting.Results Compared with the DOX-CM group,the LVIDs and LVIDd of the MaFGF-NP+UTMD group were significantly reduced,and LVEF and LVFS were significantly increased;TUNEL staining was used to detect apoptotic cells in MaFGF-NP+UTMD group significantly reduced;The ratio of pAKT/AKT and BAX content in the MaFGF-NP+UTMD group decreased and the BCL-2 content increased comparing with the DOX-CM group.Conclusion MaFGF-NP combined with UTMD can effectively prevent myocardial injury caused by doxorubicin.The mechanism may be that MaFGF reduces cardiomyocyte apoptosis caused by doxorubicin.

关 键 词：纳米脂质体 超声微泡 酸性成纤维细胞生长因子 阿霉素心肌病 

分 类 号：R445.1[医药卫生—影像医学与核医学]