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金纳多可减少高血压心脏重塑中M1极化巨噬细胞的核因子κB信号传导。

Ginaton reduces M1-polarized macrophages in hypertensive cardiac remodeling NF-κB signaling.

作者信息

Wang Jie, Cai Enze, An Xiangbo, Wang Junjie

机构信息

Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.

Department of Cardiology, the Fifth People's Hospital of Dalian, Dalian, China.

出版信息

Front Pharmacol. 2023 Mar 13;14:1104871. doi: 10.3389/fphar.2023.1104871. eCollection 2023.

DOI:10.3389/fphar.2023.1104871
PMID:36992835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10040779/
Abstract

Macrophages play a critical role in cardiac remodeling, and dysregulated macrophage polarization between the proinflammatory M1 and anti-inflammatory M2 phenotypes promotes excessive inflammation and cardiac damage. Ginaton is a natural extract extracted from . Because of its anti-inflammatory properties, it has long been used to treat a variety of diseases. However, the role of Ginaton in modulating the diverse macrophage functional phenotypes brought on by Ang II-induced hypertension and cardiac remodeling is unknown. In the present study, we fed C57BL/6J mice in the age of eight weeks with Ginaton (300 mg/kg/day) or PBS control, and then injected Ang II (1000 ng/kg/min) or saline for 14 days to investigate the specific efficacy of Ginaton. Systolic blood pressure was recorded, cardiac function was detected by echocardiography, and pathological changes in cardiac tissue were assessed by histological staining. Different functional phenotypes of the macrophages were assessed by immunostaining. The mRNA expression of genes was assessed by qPCR analysis. Protein levels were detected by immunoblotting. Our results showed that Ang II infusion significantly enhanced the activation and infiltration of macrophages with hypertension, cardiac insufficiency, myocardial hypertrophy, fibrosis and M1 phenotype macrophages compared with the saline group. Instead, Ginaton attenuated these effects. In addition, experiments showed that Ginaton inhibited Ang II-induced activation, adhesion and migration of M1 phenotype macrophages. Our study showed that Ginaton treatment inhibits Ang II-induced M1 phenotype macrophage activation, macrophage adhesion, and mitigation, as well as the inflammatory response leading to impaired and dysfunctional hypertension and cardiac remodeling. Gianton may be a powerful treatment for heart disease.

摘要

巨噬细胞在心脏重塑中起关键作用,促炎M1型和抗炎M2型表型之间的巨噬细胞极化失调会促进过度炎症反应和心脏损伤。金纳多是从……中提取的天然提取物。由于其具有抗炎特性,长期以来一直用于治疗多种疾病。然而,金纳多在调节由血管紧张素II诱导的高血压和心脏重塑所带来的多种巨噬细胞功能表型方面的作用尚不清楚。在本研究中,我们给8周龄的C57BL/6J小鼠喂食金纳多(300毫克/千克/天)或PBS对照,然后注射血管紧张素II(1000纳克/千克/分钟)或生理盐水,持续14天,以研究金纳多的具体疗效。记录收缩压,通过超声心动图检测心脏功能,并通过组织学染色评估心脏组织的病理变化。通过免疫染色评估巨噬细胞的不同功能表型。通过qPCR分析评估基因的mRNA表达。通过免疫印迹检测蛋白质水平。我们的结果表明,与生理盐水组相比,输注血管紧张素II显著增强了伴有高血压、心脏功能不全、心肌肥大、纤维化的巨噬细胞的活化和浸润以及M1型表型巨噬细胞。相反,金纳多减轻了这些影响。此外,实验表明金纳多抑制血管紧张素II诱导的M1型表型巨噬细胞的活化、黏附和迁移。我们的研究表明,金纳多治疗可抑制血管紧张素II诱导的M1型表型巨噬细胞活化、巨噬细胞黏附以及减轻炎症反应,而炎症反应会导致高血压和心脏重塑受损及功能障碍。金纳多可能是一种有效的心脏病治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/c6e30d3976ca/fphar-14-1104871-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/b531486578b6/fphar-14-1104871-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/732849efd85d/fphar-14-1104871-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/1b3a7dcf3dd0/fphar-14-1104871-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/877ff04a2e58/fphar-14-1104871-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/bea1848dfc94/fphar-14-1104871-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/8dcb63faa2a9/fphar-14-1104871-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/c6e30d3976ca/fphar-14-1104871-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/b531486578b6/fphar-14-1104871-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/732849efd85d/fphar-14-1104871-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/1b3a7dcf3dd0/fphar-14-1104871-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/877ff04a2e58/fphar-14-1104871-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/bea1848dfc94/fphar-14-1104871-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/8dcb63faa2a9/fphar-14-1104871-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c1c/10040779/c6e30d3976ca/fphar-14-1104871-g007.jpg

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Cells of the Immune System in Cardiac Remodeling: Main Players in Resolution of Inflammation and Repair After Myocardial Infarction.免疫系统细胞在心脏重构中的作用:心肌梗死后炎症消退和修复的主要参与者。
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