Assessment of ursolic acid effect on in vitro model of cardiac fibrosis

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2024-08-30 DOI:10.1016/j.tiv.2024.105924

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引用次数: 0

Abstract

This study aimed to evaluate the effects of ursolic acid (UA) on Angiotensin II (Ang II)-treated neonatal rat cardiac fibroblasts (rCFs) as an in vitro model of cardiac fibrosis. The rCFs were isolated from two-day-old neonatal rats. An in vitro model of cardiac fibrosis was established using 500 nm Ang II treatment for 48 h. The cells were then treated with 5 and 10 μM of UA for 24 and 48 h. Masson's trichrome staining, hydroxyproline content assay, scratch assay, apoptosis assay, measurements of superoxide dismutase (SOD) and malondialdehyde (MDA) levels, real-time PCR, immunocytology and western blotting, were employed to assess the impact of UA. Ang II induced fibrosis in rCFs, as evidenced by the examination of various fibrotic markers. Upon treatment with 5 and 10 μM of UA, the amount of fibrosis in Ang II-treated rCFs was significantly decreased, so that the hydroxyproline concentration was reduced to 0.3 and 0.7 times, respectively. The RNA expression of the Col1a1, Col3a1, Tgfb1, Acta2 and Mmp2 genes had a decrease as well as Nrf2 and HO-1 had an increase after UA treatment. UA could lessen the harmful effects of cardiac fibrosis in a dose- and time-dependent manner, due to its antiapoptotic, antioxidant and cardioprotective properties. This suggests the potential of UA for treatment of cardiac fibrosis.

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评估熊果酸对体外心脏纤维化模型的影响

本研究旨在评估熊果酸（UA）对血管紧张素 II（Ang II）处理的新生大鼠心脏成纤维细胞（rCFs）的影响，将其作为心脏纤维化的体外模型。rCFs是从两天大的新生大鼠体内分离出来的。用 500 nm Ang II 处理 48 小时，建立了心脏纤维化的体外模型。然后用 5 和 10 μM 的 UA 处理细胞 24 和 48 小时。采用马森三色染色法、羟脯氨酸含量测定法、划痕法、细胞凋亡测定法、超氧化物歧化酶（SOD）和丙二醛（MDA）水平测定法、实时 PCR、免疫细胞学和 Western 印迹法评估 UA 的影响。血管紧张素 II 会诱导 rCFs 纤维化，各种纤维化标志物的检测就是证明。经 5 和 10 μM UA 处理后，经 Ang II 处理的 rCFs 的纤维化量明显减少，羟脯氨酸浓度分别降低至 0.3 和 0.7 倍。UA治疗后，Col1a1、Col3a1、Tgfb1、Acta2和Mmp2基因的RNA表达量减少，Nrf2和HO-1基因的表达量增加。UA具有抗心肌凋亡、抗氧化和保护心脏的作用，能以剂量和时间依赖的方式减轻心脏纤维化的有害影响。这表明 UA 具有治疗心脏纤维化的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.