超声微泡靶向递送MaFGF改善糖尿病心肌病大鼠左心室收缩功能的初步实验研究  

MaF GF delivered by ultrasound-targeted microbubble destruction technique improves left ventricular function in rats with diabetic cardiomyopathy

作　　者：迟婷婷 滕银燕[1] 孙玮明[1] 林海霞[1] 郑磊[1] 田新桥[2] CHI Tingting;TENG Yinyan;SUN Weiming(Department of Ultrasonography,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第一医院超声影像科,325000 [2]河南省人民医院超声科

出　　处：《浙江医学》2019年第24期2576-2579,2587,I0003,共6页Zhejiang Medical Journal

基　　金：国家自然科学基金资助项目（81571696）;温州市公益性科技计划项目（Y20170049、Y20170311)

摘　　要：目的探讨应用超声靶向微泡击破技术(UTMD)递送改构型酸性成纤维细胞生长因子(MaFGF)对改善糖尿病心肌病(DCM)大鼠的左心室收缩功能的价值。方法将75只健康雄性SD大鼠适应性饲养1周后,采用随机数字表法挑选15只作为正常对照组(N组),不做干预,余60只经腹腔注射链脲佐菌素(STZ)建立Ⅰ型糖尿病模型(70mg/kg),将造模成功52只大鼠继续饲养8周,继而采用随机数字表法分为4组(DCM模型组、MaFGF组、MaFGF-SonoVue组及MaFGF-SonoVue+UTMD组,每组13只)。各组分别给予相应干预4周,然后对所有大鼠行常规超声心动图及速度向量成像(VVI)检查,测量并比较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)、左心室短轴缩短率(LVFS)、乳头肌水平左心室壁各节段平均径向峰值速度(Vs)、径向应变(Sr)及径向应变率(SRr)差异。随后处死大鼠取心肌组织,TUNEL染色计算心肌组织凋亡指数(AI),天狼星红染色计算心肌血管周围胶原面积与血管腔面积之比(PVCA/LA)。结果干预4周后,与N组比较,DCM组LVIDd及LVIDs均增加(均P<0.05),LVEF、LVFS、Vs、Sr及SRr均明显减低(均P <0.05),AI和PVCA/LA均明显升高(均P <0.05);与DCM组比较,MaFGF-SonoVue+UTMD组LVIDd及LVIDs均降低(均P<0.05);与DCM组及其他治疗组比较,MaFGF-SonoVue+UTMD组LVEF、LVFS、Vs、Sr及SRr均明显增高(均P<0.05),而AI、PVCA/LA均明显降低(均P<0.05)。结论应用UTMD技术递送MaFGF对改善DCM大鼠左心室收缩功能有重要价值,UTMD靶向传输系统可明显提高药效。Objective To investigate the effects of modified acidic fibroblast growth factor(MaFGF) delivered by ultrasound targeted microbubble destruction(UTMD) technique on left ventricular function in rats with diabetic cardiomyopathy(DCM). Methods DCM model was established in male SD rats by intraperitoneal injection of streptozotocin(STZ, 70 mg/kg). Fifty two DCM rats were divided into DCM group, MaFGF group, MaFGF-SonoVue group and MaFGF-SonoVue+UTMD group(n=13 in each group) and treated correspondingly for 4 wks. The Untreated SD rats were used as normal controls(N group). The conventional echocardiography and the velocity vector imaging(VVI) were performed in all groups. Left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS) were measured by echocardiography. The segmental mean peak systolic radial velocity(Vs), systolic radial strain(Sr) and systolic radial strain rate(SRr) of six walls at the papillary muscle level were measured in left ventricular short-axis view by VVI. The myocardial tissues were stained with TUNEL and Sirius red staining;the apoptosis index(AI), the perivascular collagen area and lumen area ratio(PVCA/LA) were calculated. Results After 4 weeks of interventions, the LVEF, LVFS, Vs, Sr and SRr of the DCM group were significantly decreased(P<0.05), while the LVIDd, LVIDs, AI and PVCA/LA increased compared with those of the normal group(P<0.05). The LVIDd, LVIDs, AI and PVCA/LA were decrease,while the LVEF, LVFS, Vs, Sr and SRr of the MaFGF-SonoVue+UTMD group were significantly increased compared with those of the DCM group and the other treatment groups(P<0.05). Conclusion MaFGF-SonoVue delivered by UTMD is of great value to improve the left ventricular systolic function of DCM rats, indicating that the UTMD technique can significantly improve the drug efficacy.

关 键 词：超声心动图 酸性成纤维细胞生长因子 糖尿病心肌病 大鼠 

分 类 号：R54[医药卫生—心血管疾病]