靶向超声微泡爆破技术结合新型aFGF肝素化纳米脂质体对糖尿病心肌病的早期预防作用  

Advanced interfere prevention of diabetic cardiomyopathy rats by acid fibroblast growth factor-loaded heparin-modified nano-liposomes and ultrasound-targeted microbubble destruction technique

作　　者：张明 俞燕华 陈元娜 徐锦龙 陈梦嘉 俞璐 王井玲 马卫成 Zhang Ming;Yu Yanhua;Chen Yuanna;Xu Jinlong;Chen Mengjia;Yu Lu;Wang Jingling;Ma Weicheng(Department of Pharmacy, 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：《中华内分泌外科杂志》2018年第6期459-463,共5页Chinese Journal of Endocrine Surgery

基　　金：国家自然科学基金(81360195);宁波市自然基金(2017A610254);浙江省医药卫生科技项目(2019319849).

摘　　要：目的研究酸性成纤维细胞生长因子(acidic fibroblast growth factor,aFGF)肝素化纳米脂质体结合超声靶向微泡爆破技术(ultrasound-targeted microbubble destruction,UTMD)对糖尿病心肌病(diabetic cardiomyopathy,DCM)的早期预防效果。方法健康雄性Sprague Dawley大鼠75只,随机数字表法随机选择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(70mg/kg)建立糖尿病模型,将糖尿病大鼠又随机分成糖尿病模型组、aFGF溶液干预组、aFGF肝素化纳米脂质体干预组及aFGF肝素化纳米脂质体+UTMD干预组,每组15只。药物干预前及干预12周后均用速度向量成像(velocity vector imaging,VVI)评价大鼠心功能,测定收缩期径向速度(the segmental mean peak systolic radial velocity,Vs)、收缩期平均切向应变(systolic circumferential strain,Sc)及径向应变(systolic circumferential strain rate,SRc)。处死大鼠取出心肌组织,Westernblot分析心肌aFGF含量。通过Masson胶原染色及Tunel凋亡染色测定心肌胶原容积分数(collagen volume fraction,CVF)及心肌细胞凋亡指数(apoptosis index,AI)。结果aFGF肝素化纳米脂质体形态圆整,包封率高达(89.4±1.2)%且稳定性好。Westernblot分析证实:相比于其他各个实验组,应用aFGF肝素化纳米脂质体结合UTMD预防组大鼠心肌aFGF含量显著升高(P<0.05)。超声心功能结果显示:相比于其他实验组,应用aFGF肝素化纳米脂质体结合UTMD干预组的心脏Vs、Sc及SRc的绝对值显著升高(P<0.05)。同时Masson胶原染色及Tunel凋亡染色证实:相比于其他实验组,应用aFGF肝素化纳米脂质体结合UTMD技术干预组大鼠心肌CVF值及AI值显著下降(P<0.05),接近正常对照组水平。结论aFGF肝素化纳米脂质体联合UTMD技术能有效预防糖尿病引起的心肌结构及功能的病变,该技术有望成为预防糖尿病心肌病的新方案。Objective To investigate the advanced preventive effect of acid fibroblast growth factor (aFGF) on diabetic cardiomyopathy (DCM) by using heparin-modified nano-liposomes combined with ultrasound-targeted microbubble destruction technique (UTMD) . Methods aFGF-loaded nano-liposomes (aFGF-lips) were prepared by lyophilization technique. Type Ⅰ diabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) in male SD rats. Before and twelve weeks after intervention, all rats underwent the transthoracic echocardiography. The segmental mean peak systolic radial velocity (Vs) , systolic circumferential strain (Sc) , and systolic circumferential strain rate (SRc) were measured. The expression of aFGF in DCM rats was detected by western blot. The rats were sacrificed and myocardial tissue were stained with masson staining and Tunel staining to quantify myocardial collagen fraction (CVF) and cardiac myocyte apoptosis index (AI) . Results aFGF-lips showed good morphology and aFGF encapsulation efficiency (89.4±1.2) % with high stability. From the animal experiments, the echocardiographic indexes including Vs, Sc and SRc had significantly improvements over DM group (P<0.05) and all other treatment group (P<0.05) . The Masson’s trichrome staining demonstrated that CVF was significantly higher in DM group than in the control group and was significantly lower in the aFGF-loaded nano-liposome+UTMD group than other groups (all P<0.05) . The TUNEL results showed that AI was significantly higher in DM group than in the control group and was significantly lower in aFGF-loaded nano-liposome+UTMD group than other groups (all P<0.05) . Conclusion aFGF nano-liposome combining with UTMD technique can improve the functions and pathologies of the hearts in type 1 diabetes mellitus model, which might provide a novel technique for aFGF in DCM prevention.

关 键 词：糖尿病心肌病 酸性成纤维细胞生长因子 超声靶向微泡爆破技术 肝素化纳米脂质体 

分 类 号：R587.2[医药卫生—内分泌]