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异甜菊醇钠对腹主动脉缩窄大鼠心功能和心肌重构的保护作用。

The protective effect of isosteviol sodium on cardiac function and myocardial remodelling in transverse aortic constriction rat.

机构信息

Institute of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China.

出版信息

J Cell Mol Med. 2021 Jan;25(2):1166-1177. doi: 10.1111/jcmm.16182. Epub 2020 Dec 17.

Abstract

Pathological hypertrophy contributes to heart failure and there is not quite effective treatment to invert this process. Isosteviol has been shown to protect the heart against ischaemia-reperfusion injury and isoproterenol-induced cardiac hypertrophy, but its effect on pressure overload-induced cardiac hypertrophy is still unknown. Pressure overload induced by transverse aortic constriction (TAC) causes cardiac hypertrophy in rats to mimic the pathological condition in human. This study examined the effects of isosteviol sodium (STVNa) on cardiac hypertrophy by the TAC model and cellular assays in vitro. Cardiac function test, electrocardiogram analysis and histological analysis were conducted. The effects of STVNa on calcium transient of the adult rat ventricular cells and the proliferation of neonatal rat cardiac fibroblasts were also studied in vitro. Cardiac hypertrophy was observed after 3-week TAC while the extensive cardiac dysfunction and electronic remodelling were observed after 9-week TAC. Both STVNa and sildenafil (positive drug) treatment reversed the two process, but STVNa appeared to be more superior in some aspects and did not change calcium transient considerably. STVNa also reversed TAC-induced cardiac fibrosis in vivo and TGF-β1-induced fibroblast proliferation in vitro. Moreover, STVNa, but not sildenafil, reversed impairment of the autonomic nervous system induced by 9-week TAC.

摘要

病理性心肌肥厚可导致心力衰竭,目前尚无有效的治疗方法来逆转这一过程。异甜醇已被证明可保护心脏免受缺血再灌注损伤和异丙肾上腺素诱导的心肌肥厚,但它对压力超负荷诱导的心肌肥厚的影响尚不清楚。通过横主动脉缩窄(TAC)引起的压力超负荷会导致大鼠心肌肥厚,从而模拟人类的病理状况。本研究通过 TAC 模型和体外细胞实验研究了异甜醇钠(STVNa)对心肌肥厚的影响。进行了心脏功能测试、心电图分析和组织学分析。还研究了 STVNa 对成年大鼠心室细胞钙瞬变和新生大鼠心肌成纤维细胞增殖的影响。在 3 周 TAC 后观察到心肌肥厚,而在 9 周 TAC 后观察到广泛的心脏功能障碍和电子重塑。STVNa 和西地那非(阳性药物)治疗均逆转了这两个过程,但 STVNa 在某些方面似乎更优越,对钙瞬变影响不大。STVNa 还可逆转体内 TAC 诱导的心肌纤维化和 TGF-β1 诱导的成纤维细胞增殖。此外,STVNa 可逆转 9 周 TAC 引起的自主神经系统损伤,但西地那非不能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0449/7812303/5ca5494b13de/JCMM-25-1166-g001.jpg

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