FGF1纳米脂质体结合超声靶向微泡爆破技术治疗糖尿病心肌病的实验研究  

Therapeutic effect of combined use of FGF1-loaded nano-liposomes and ultrasound-targeted microbubble destruction technique on treating rats with experimental diabetic cardiomyopathy

作　　者：张明 赵应征 马卫成 徐锦龙 王井玲 陈梦嘉 俞璐 陈元娜 Zhang Ming Zhao Yingzheng Ma Weicheng Xu Jinlong Wang Jingling Chen Mengjia Yu Lu Chen Yuanna(Ningbo Yinzhou Second Hospital, Ningbo 315100, China)

机构地区：[1]宁波市鄞州第二医院药剂科,315100

出　　处：《中华心血管病杂志》2017年第5期427-433,共7页Chinese Journal of Cardiology

基　　金：国家自然科学基金（81360195）

摘　　要：目的 研究酸性成纤维细胞生长因子1（FGF1）纳米脂质体结合超声靶向微泡爆破技术（UTMD）对于糖尿病心肌病（DCM）的治疗效果.方法 健康雄性Sprague Dawley大鼠75只,随机数字表法选择15只作为正常对照组（对照组）,其余大鼠腹腔注射链脲佐菌素（70 mg/kg）建立糖尿病模型,成模后继续饲养16周,通过超声心动图筛选出DCM大鼠模型.将DCM大鼠按随机数字表法分为4组,即DCM模型组（DCM组,给予生理盐水治疗）、FGF1溶液治疗组（FGF1溶液组）、FGF1纳米脂质体治疗组（FGF1纳米脂质体组）和FGF1纳米脂质体＋UTMD治疗组（FGF1纳米脂质体＋UTMD组）,每组15只.采用水包水型乳化法结合冷冻干燥技术制备FGF1载药纳米脂质体.药物干预2周再继续饲养2周后,采用心导管评价各组大鼠心功能.处死大鼠后取出心肌组织,分别通过Masson胶原染色、TUNEL凋亡染色及CD31免疫组织化学染色测定各组大鼠心肌胶原容积分数（CVF）、心肌凋亡指数及心肌微血管密度（MVD）.结果 （1）FGF1纳米脂质体质量评价结果：扫描电镜观察空白及载药纳米脂质体均呈标准的椭球形,分散均匀且包封率高稳定性好.（2）各组大鼠心功能的心导管检测结果：FGF1纳米脂质体＋UTMD组大鼠左心室收缩末期压力、左心室内压最大上升和下降速率均明显高于DCM组、FGF1溶液组和FGF1纳米脂质体组（P均＜0.05）,而左心室舒张末期压力则明显低于DCM组、FGF1溶液组和FGF1纳米脂质体组（P均＜0.05）.（3）各组大鼠心肌CVF的测定结果：DCM组大鼠心肌CVF明显大于对照组（P＜0.05）.FGF1溶液组、FGF1纳米脂质体组和FGF1纳米脂质体＋UTMD组大鼠心肌CVF均明显小于DCM组（P均＜0.05）.而FGF1纳米脂质体＋UTMD组大鼠心肌CVF则进一步小于FGF1溶液组和FGF1纳米脂质体组（P均＜0.05）.（4）各组大鼠心肌组织MVD的检测结果：DCM组大鼠心肌组织MVD明显�Objective The therapeutic effect of acid fibroblast growth factor 1 （FGF1） on rats with diabetic cardiomyopathy （DCM） was evaluated by using nano-liposomes combined with ultrasound-targeted microbubble destruction technique （UTMD）.Methods The FGFl-loaded nano-liposomes were prepared by water-in-water emulsion method combined with lyophilization technique.Type Ⅰ diabetes model was induced by intraperitoneal injection of streptozotocin （STZ,70 mg/kg） in 60 male SD rats.Sixteen weeks later,diabetic rats were randomly divided into：placebo group （saline treatment）,FGF1 group,FGF1-loaded nano-liposomes group,and FGF1-loaded nano-liposomes plus UTMD group （n =15 each）.After two weeks of intervention followed by 2 weeks intervention stop,all rats underwent cardiac catheterization,and the left ventricular end-systolic pressure （LVESP）,left ventricular end-diastolic pressure （LVEDP） and the maximal increase/decrease rate of left ventricular pressure （LV ± dp/dtmax） were measured.Then,the rats were sacrificed and myocardial tissue were obtained for Masson trichrome staining,TUNEL apoptotic staining and CD31 immunohistochemistry staining to quantify myocardial collagen fraction （CVF）,cardiac myocyte apoptotic index and myocardial microvascular density （MVD）.Results （1） Scanning electron microscope results revealed good morphology and FGF1 encapsulation efficiency （84.3 ± 2.8） ％ with high stability and dispensability of FGF1 loaded nano-liposomes.（2）The hemodynamic evaluation showed that LVESP,LV ＋ dp/dtmax and LV-dp/dtmax were all significantly higher,while LVEDP was significantly lower in the FGF1-loaded nano-liposome ＋ UTMD group than in DCM group,FGF1 solution group,and FGF1 nano-liposome group（all P ＜0.05）.（3）The Masson trichrome staining demonstrated that CVF was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome ＋ UTMD group than in DCM group,FGF1 solution group,and FGF1

关 键 词：糖尿病心肌病 成纤维细胞生长因子1 脂质体 超声微泡靶向爆破技术 

分 类 号：R542.2[医药卫生—心血管疾病] R587.2[医药卫生—内科学]