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研究山柰酚在人 THP-1 巨噬细胞中抗动脉粥样硬化作用的分子机制。

Investigation of the Molecular Mechanisms Underlying the Antiatherogenic Actions of Kaempferol in Human THP-1 Macrophages.

机构信息

Biochemistry Department, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

Cell Culture Unit and Experimental Biochemistry Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah 21589, Saudi Arabia.

出版信息

Int J Mol Sci. 2022 Jul 5;23(13):7461. doi: 10.3390/ijms23137461.

DOI:10.3390/ijms23137461
PMID:35806463
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9267302/
Abstract

Cardiovascular disease (CVD) is causing high mortality worldwide (World Health Organization-WHO, 2015). Atherosclerosis, the hardening and narrowing of arteries caused by the accumulation of fatty acids and lipids (cholesterol plaques), is a main reason of stroke, myocardial infarction, and angina. Present therapies for cardiovascular disease basically use statins such as β-Hydroxy β-methylglutaryl-CoA, with <70% efficacy and multiple side effects. An in vitro investigation was conducted to evaluate the impact of kaempferol, a natural medication, in an atherosclerotic cell model. We used cytotoxicity assays, Boyden chamber invasion assays, and quantitative PCR. Affymetrix microarrays were used to profile the entire transcriptome of kaempferol-treated cell lines, and Partek Genomic Suite was used to interpret the results. Kaempferol was not cytotoxic to THP-1 macrophages. In comparison to the control, kaempferol reduced monocyte migration mediated by monocyte chemotactic protein 1 (MCP-1) by 80%. The qPCR results showed a 73.7-fold reduction in MCP-1 and a 2.5-fold reduction in intercellular adhesion molecule 1 (ICAM-1) expression in kaempferol-treated cells. In interferon gamma (IFN-γ) without kaempferol and IFN-γ with kaempferol treated cells, we found 295 and 168 differentially expressed genes (DEGs), respectively. According to DEG pathway analysis, kaempferol exhibits anti-atherosclerosis and anti-inflammatory characteristics. Kaempferol is an effective and safe therapy for atherosclerosis.

摘要

心血管疾病(CVD)在全球范围内导致高死亡率(世界卫生组织-WHO,2015 年)。动脉粥样硬化是由脂肪酸和脂质(胆固醇斑块)积聚引起的动脉变硬和变窄,是中风、心肌梗死和心绞痛的主要原因。目前心血管疾病的治疗方法主要使用他汀类药物,如β-羟-β-甲基戊二酰辅酶 A,其疗效<70%,且有多种副作用。进行了一项体外研究,以评估天然药物山柰酚在动脉粥样硬化细胞模型中的作用。我们使用细胞毒性测定、Boyden 室侵袭测定和定量 PCR。Affymetrix 微阵列用于分析山柰酚处理的细胞系的整个转录组,并用 Partek 基因组套件解释结果。山柰酚对 THP-1 巨噬细胞没有细胞毒性。与对照组相比,山柰酚使单核细胞趋化蛋白 1(MCP-1)介导的单核细胞迁移减少了 80%。qPCR 结果显示,MCP-1 的表达减少了 73.7 倍,细胞间黏附分子 1(ICAM-1)的表达减少了 2.5 倍。在无山柰酚的干扰素 γ(IFN-γ)和有山柰酚的 IFN-γ处理的细胞中,我们分别发现了 295 和 168 个差异表达基因(DEGs)。根据 DEG 通路分析,山柰酚具有抗动脉粥样硬化和抗炎特性。山柰酚是一种有效且安全的动脉粥样硬化治疗方法。

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