艾司洛尔逆转高血压大鼠早期左室肥厚：亚细胞器表型的作用

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Baezac Early reversal cardiac with esmolol in hypertensive rats: the role of subcellular organelle phenotype

背景与目的

我们的研究小组先前已经证明，艾司洛尔短期治疗（48小时）可以减轻自发性高血压大鼠（SHRs）的左室肥厚（LVH）。然而我们并不知道如何解释这一影响的机制。本研究的目的是评估亚细胞器表型在艾司洛尔短期治疗后早期心脏逆转中的作用。

方  法

14月龄雄性SHRs随机分为艾司洛尔组（300μg/kg/min）（SHR-e）或生理盐水组（SHR）。年龄匹配的雄性wistar-kyoto大鼠（WKY）作为对照。治疗48小时后，对心脏组织（左心室）进行超微结构分析。用电子显微镜观察各组心肌细胞亚细胞器的超微结构重塑。

结  果

SHR组线粒体和亚细胞器（细胞质和细胞核、肌原纤维结构、线粒体结构、z盘、闰盘、t系统和终池）的形态和体视学改变均较WKY组显著，细胞外基质（胶原）的变化也较WKY组显著。艾司洛尔显著改善SHR组线粒体形态和体视学，减少细胞器表型异常，但细胞外基质无明显变化。有趣的是，SHR-E的线粒体参数（规则因子、椭球形状因子和体积密度）和亚细胞器官的所有参数均恢复正常。

结  论

我们的研究结果表明，艾司洛尔短期治疗后左室肥厚逆转与亚细胞器表型逆转有关。

原始文献摘要

Begoña Quintana-Villamandosa,b, María Jesús Delgado-Martosc,d, Emilio Delgado ，Baezac Early reversal cardiac with esmolol in hypertensive rats: the role of subcellular organelle phenotype[J] Pharmacol Rep 2019 Jun 29;71(6) DOI：10.1016/j.pharep.2019.06.013  

Background: Our group has previously shown that short-term treatment (48 hours) with esmolol reduces left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs). However, we do not know the mechanism that explain this effect. The aim of this study was to assess the role that the subcellular organelle phenotype plays in early cardiac reverse after short-term treatment with esmolol. 

Methods: 14-month-old male SHRs were randomly assigned to receive esmolol (300 μg/kg/min)(SHR-E) or vehicle (SHR). Age-matched male Wistar-Kyoto rats (WKY) served as controls. After 48 hours of treatment, an ultrastructural analysis of heart tissue (left ventricle) was performed. We studied cardiomyocyte ultrastructural remodeling of subcellular organelles by electronic microcopy in all groups.

Results: SHR group showed significant morphometric and stereological changes in mitochondria and subcellular organelles (cytoplasm and nucleus, myofibril structure, mitochondria structure, Z-Disk, intercalated disk, T-system and cystern), and also changes in the extracellular matrix (collagen) with respect to WKY group. Esmolol  significantly improved the morphology and stereology mitochondrial, reduced the organelle phenotype abnormalities but no produced changes in the extracellular matrix with respect to SHR group. Interesantly, parameters of mitochondria (regularity factor, ellipsoidal form factor and density of volume), and all parameters of subcellular  organelles returned to the normality in SHR-E. 

Conclusion: Our results show that left ventricular hypertrophy reversal after short-term  treatment with esmolol is associated with reversal of subcellular organelle phenotype.

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翻译：冯玉蓉    编辑：何幼芹   审校：王贵龙