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腺病毒介导 miR-199a 纳米粒对心力衰竭大鼠 HSP27、HSP70 和可溶性糖蛋白表达的影响。

Efficacy of Adenovirus-mediated, miR-199a Nanoparticles on Expression of HSP27, HSP70, and Soluble Glycoprotein in Rats with Heart Failure.

出版信息

Altern Ther Health Med. 2023 Apr;29(3):146-152.

PMID:36735713
Abstract

CONTEXT

Heart failure (HF) refers to abnormal changes in the function of the body's heart pump under the action of a variety of pathogenic factors. Due to the complex etiology and course of HF, current research on its etiology and pathogenesis hasn't yet reached a clear conclusion. So, there are many manifestations of heart failure in patients, and there are also many changes in the treatment.

OBJECTIVES

The study intended to evaluate the efficacy of adenovirus-mediated miR-199a nanoparticles (NPs) for heart failure (HF).

DESIGN

The research team performed an animal study.

SETTING

The study took place at Shanghai Pudong Hospital at Fudan University Pudong Medical Center in Shanghai, China.

ANIMALS

The animals were 40 healthy, adult, male, Sprague-Dawley (SD) rats. They were specific pathogen-free (SPF) grade SD rats, all weighing about 280 g and aged 7-8 weeks.

INTERVENTION

The research team: (1) induced HF using coronary artery ligation and established different HF models and (2) randomly divided the rats into two groups with 20 rats in each group-an experimental group, which received high-dose, microR-199a (miR-199a) NPs, and a control group, which received low-dose miR-199a NPs. The treatments occurred for seven days after the induction of HF.

OUTCOME MEASURES

At baseline and postintervention, the research team measured the left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), diastolic and systolic left ventricular anterior wall (LVAW) thickness, left ventricular posterior wall (LVPW) thickness, and expression of heat shock protein 27 (HSP27), HSP70, soluble glycoprotein 130 (SGP130). The team analyzed and studied the effects of the adenovirus-mediated miR-199a NP on that expression, based on the above indicators.

RESULTS

The miR-199a prepared with NPs had good specificity through observation. The expression of HSP27, SGP130 was significantly downregulated in the experimental group as compared to the control group (P < .05) and HSP70 was upregulated in the experimental group as compared to the control group (P < .05). The expression decreased, or increased, with an increase in the cardiac-function classification, with substantial differences between the control and experimental groups. Expression levels of HSP27, HSP70, and SGP in the experimental group were negatively correlated with those of controls and negatively correlated with the left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), and left ventricular ejection fraction (LVEF).

CONCLUSIONS

NP had good specificity. The miR-199a NP downregulated levels of HSP, which had a certain protective effect against HF and had a high clinical-adoption and promotion value.

摘要

背景

心力衰竭(HF)是指在多种致病因素作用下,机体心脏泵功能的异常改变。由于 HF 的病因和病程复杂,目前对其病因和发病机制的研究尚未得出明确结论。因此,HF 患者有很多种临床表现,治疗方法也有很多变化。

目的

本研究旨在评估腺病毒介导的 miR-199a 纳米颗粒(NPs)治疗心力衰竭(HF)的疗效。

设计

该研究团队进行了一项动物研究。

地点

中国上海复旦大学附属浦东医院浦东医疗中心。

动物

40 只健康、成年、雄性 Sprague-Dawley(SD)大鼠。它们是无特定病原体(SPF)级 SD 大鼠,均重约 280g,年龄 7-8 周。

干预

研究团队:(1)通过冠状动脉结扎诱导 HF,并建立不同的 HF 模型;(2)将大鼠随机分为两组,每组 20 只,实验组给予高剂量 miR-199a NPs,对照组给予低剂量 miR-199a NPs。HF 诱导后 7 天进行治疗。

观察指标

在基线和干预后,研究团队测量了左心室射血分数(LVEF)、左心室舒张末期直径(LVEDD)、左心室收缩末期直径(LVESD)、舒张期和收缩期左心室前壁(LVAW)厚度、左心室后壁(LVPW)厚度和热休克蛋白 27(HSP27)、HSP70、可溶性糖蛋白 130(SGP130)的表达。根据上述指标,分析和研究了腺病毒介导的 miR-199a NP 对其表达的影响。

结果

通过观察发现,用 NPs 制备的 miR-199a 具有良好的特异性。与对照组相比,实验组 HSP27 和 SGP130 的表达明显下调(P<0.05),HSP70 表达上调(P<0.05)。随着心功能分类的增加,HSP27、HSP70 和 SGP130 的表达降低或增加,对照组与实验组之间存在显著差异。实验组 HSP27、HSP70 和 SGP 的表达水平与对照组呈负相关,与左心室舒张末期直径(LVEDD)、左心室收缩末期直径(LVESD)和左心室射血分数(LVEF)呈负相关。

结论

NP 具有良好的特异性。miR-199a NP 下调 HSP 水平,对 HF 具有一定的保护作用,具有较高的临床应用和推广价值。

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