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超声介导的载有FGF1的纳米脂质体联合微泡空化对糖尿病心肌病预防作用的评估

Assessment of the Preventive Effect Against Diabetic Cardiomyopathy of FGF1-Loaded Nanoliposomes Combined With Microbubble Cavitation by Ultrasound.

作者信息

Zheng Lei, Shen Chuan-Li, Li Jian-Min, Ma Yu-Lei, Yan Ning, Tian Xin-Qiao, Zhao Ying-Zheng

机构信息

Department of Ultrasonography, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Department of Ultrasonography of Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, China.

Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Front Pharmacol. 2020 Jan 10;10:1535. doi: 10.3389/fphar.2019.01535. eCollection 2019.

Abstract

Acidic fibroblast growth factor (FGF1) has great potential in preventing diabetic cardiomyopathy. This study aimed to evaluate the preventive effect of FGF1-loaded nanoliposomes (FGF1-nlip) combined with ultrasound-targeted microbubble destruction (UTMD) on diabetic cardiomyopathy (DCM) using ultrasound examination. Nanoliposomes encapsulating FGF1 were prepared by reverse phase evaporation. DM model rats were established by intraperitoneal injection of streptozotocin (STZ), and different forms of FGF1 (FGF1 solution, FGF1-nlip, and FGF1-nlip+UTMD) were used for a 12-week intervention. According to the transthoracic echocardiography and velocity vector imaging (VVI) indexes, the LVEF, LVFS, and VVI indexes (Vs, Sr, SRr) in the FGF1-nlip+UTMD group were significantly higher than those in the DM model group and other FGF1 intervention groups. From the real-time myocardial contrast echocardiography (RT-MCE) indexes, the FGF1-nlip+UTMD group A and A×β showed significant differences from the DM model group and other FGF1 intervention groups. Cardiac catheter hemodynamic testing, CD31 immunohistochemical staining, and electron microscopy also confirmed the same conclusion. These results confirmed that the abnormalities, including myocardial dysfunction and perfusion impairment, could be suppressed to different extents by the twice weekly FGF1 treatments for 12 consecutive weeks (free FGF1, FGF1-nlip, and FGF1-nlip+UTMD), with the strongest improvements observed in the FGF1-nlip+UTMD group. In conclusion, the VVI and RT-MCE techniques can detect left ventricular systolic function and perfusion changes in DM rats, providing a more effective experimental basis for the early detection and treatment evaluation of DCM, which is of great significance for the prevention of DCM.

摘要

酸性成纤维细胞生长因子(FGF1)在预防糖尿病性心肌病方面具有巨大潜力。本研究旨在通过超声检查评估负载FGF1的纳米脂质体(FGF1-nlip)联合超声靶向微泡破坏(UTMD)对糖尿病性心肌病(DCM)的预防作用。采用逆相蒸发法制备包裹FGF1的纳米脂质体。通过腹腔注射链脲佐菌素(STZ)建立糖尿病模型大鼠,并使用不同形式的FGF1(FGF1溶液、FGF1-nlip和FGF1-nlip+UTMD)进行为期12周的干预。根据经胸超声心动图和速度向量成像(VVI)指标,FGF1-nlip+UTMD组的左室射血分数(LVEF)、左室短轴缩短率(LVFS)和VVI指标(Vs、Sr、SRr)显著高于糖尿病模型组和其他FGF1干预组。从实时心肌对比超声心动图(RT-MCE)指标来看,FGF1-nlip+UTMD组的A和A×β与糖尿病模型组和其他FGF1干预组存在显著差异。心脏导管血流动力学检测、CD31免疫组织化学染色和电子显微镜检查也证实了相同的结论。这些结果证实,连续12周每周两次的FGF1治疗(游离FGF1、FGF1-nlip和FGF1-nlip+UTMD)可在不同程度上抑制包括心肌功能障碍和灌注受损在内的异常情况,其中FGF1-nlip+UTMD组的改善最为明显。总之,VVI和RT-MCE技术可检测糖尿病大鼠左心室收缩功能和灌注变化,为糖尿病性心肌病的早期检测和治疗评估提供更有效的实验依据,对预防糖尿病性心肌病具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae91/6967235/b343272b99e9/fphar-10-01535-g001.jpg

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