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超声靶向微泡破坏促进糖尿病心肌病大鼠模型心肌血管生成和功能改善。

Ultrasound-targeted microbubble destruction promotes myocardial angiogenesis and functional improvements in rat model of diabetic cardiomyopathy.

机构信息

Department of Ultrasonography, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Henan University People's Hospital, NO. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.

School of Pharmacy, Xinxiang Medical University, Xinxiang, 453002, Henan, China.

出版信息

BMC Cardiovasc Disord. 2021 Jan 7;21(1):21. doi: 10.1186/s12872-020-01815-4.

Abstract

BACKGROUND

Microvascular insufficiency plays an important role in the development of diabetic cardiomyopathy (DCM), therapeutic angiogenesis has been mainly used for the treatment of ischemic diseases. This study sought to verify the preclinical performance of SonoVue microbubbles (MB) combined ultrasound (US) treatment on myocardial angiogenesis in the rat model of DCM and investigate the optimal ultrasonic parameters.

METHODS

The male Sprague-Dawley (SD) rats were induced DCM by streptozotocin through intraperitoneal injecting and fed with high-fat diet. After the DCM model was established, the rats were divided into the normal group, DCM model group, and US + MB group, while the US + MB group was divided into four subsets according to different pulse lengths (PL) (8 cycles;18 cycle;26 cycle; 36 cycle). After all interventions, all rats underwent conventional echocardiography to examine the cardiac function. The rats were sacrificed and myocardial tissue was examined by histology and morphometry evaluations to detect the myocardial protective effect of SonoVue MBs using US techniques.

RESULTS

From morphologic observation and echocardiography, the DCM rats had a series of structural abnormalities of cardiac myocardium compared to the normal rats. The US-MB groups exerted cardioprotective effect in DCM rats, improved reparative neovascularization and increased cardiac perfusion, while the 26 cycle group showed significant therapeutic effects on the cardiac functions in DCM rats.

CONCLUSION

This strategy using SonoVue MB and US can improve the efficacy of angiogenesis, even reverse the progress of cardiac dysfunction and pathological abnormalities, especially using the 26 cycle parameters. Under further study, this combined strategy might provide a novel approach for early intervention of DCM in diabetic patients.

摘要

背景

微血管功能不全在糖尿病心肌病(DCM)的发展中起着重要作用,治疗性血管生成主要用于治疗缺血性疾病。本研究旨在验证 SonoVue 微泡(MB)联合超声(US)治疗在 DCM 大鼠模型中心肌血管生成中的临床前表现,并探讨最佳超声参数。

方法

雄性 Sprague-Dawley(SD)大鼠通过腹腔注射链脲佐菌素诱导 DCM,并给予高脂饮食。DCM 模型建立后,将大鼠分为正常组、DCM 模型组和 US+MB 组,US+MB 组根据不同的脉冲长度(PL)(8 个周期;18 个周期;26 个周期;36 个周期)分为四个亚组。所有干预后,所有大鼠均进行常规超声心动图检查,评估心功能。处死大鼠,通过组织学和形态计量学评估心肌组织,使用 US 技术检测 SonoVue MB 对心肌的保护作用。

结果

从形态学观察和超声心动图来看,与正常大鼠相比,DCM 大鼠的心肌结构有一系列异常。US-MB 组对 DCM 大鼠发挥了心脏保护作用,改善了修复性新生血管形成并增加了心脏灌注,而 26 个周期组对 DCM 大鼠的心脏功能表现出显著的治疗效果。

结论

该使用 SonoVue MB 和 US 的策略可以提高血管生成的疗效,甚至逆转心脏功能障碍和病理异常的进展,特别是使用 26 个周期的参数。在进一步的研究中,这种联合策略可能为糖尿病患者的 DCM 早期干预提供一种新的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e457/7791842/6896fed492e3/12872_2020_1815_Fig1_HTML.jpg

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