β -羟基丁酸通过调节巨噬细胞极化改善糖尿病性心肌病大鼠心肌纤维化。

IF 7.4 3区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Mei He , Weiguang Luo , Shuwei Ning , Yuexin Yu , Bin Yang , Zhikun Guo
{"title":"β -羟基丁酸通过调节巨噬细胞极化改善糖尿病性心肌病大鼠心肌纤维化。","authors":"Mei He ,&nbsp;Weiguang Luo ,&nbsp;Shuwei Ning ,&nbsp;Yuexin Yu ,&nbsp;Bin Yang ,&nbsp;Zhikun Guo","doi":"10.1016/j.diabres.2025.112461","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Beta-hydroxybutyrate (BHB) has been demonstrated to enhance cardiac function in patients with diabetic cardiomyopathy (DCM), the underlying mechanism remains unclear.</div></div><div><h3>Methods</h3><div>A DCM rat model was established, BHB was administered via intraperitoneal injection. The therapeutic effects of BHB were assessed based on cardiac function, fasting glucose levels, myocardial fibrosis markers and myocardial macrophage polarization. To elucidate the mechanism of action, co-culture experiments were conducted using cardiac fibroblasts and peritoneal macrophages to evaluate collagen expression in fibroblasts and macrophage polarization under BHB treatment.</div></div><div><h3>Results</h3><div>BHB improved cardiac function in DCM rats, reduced fasting glucose levels, alleviated cardiac fibrosis and modulated macrophage polarization. After BHB treatment, the proportion of M1 macrophages decreased while that of M2 macrophages increased in the myocardium of DCM rats. Cardiac fibroblasts isolated from neonatal rats, when co-cultured with peritoneal macrophages under high-glucose conditions, exhibited altered macrophage polarization and collagen expression. High-glucose conditions promoted an increase in M1 macrophages and a decrease in M2 macrophages. BHB treatment reversed this trend by reducing M1 macrophages and promoting M2 macrophage polarization.</div></div><div><h3>Conclusions</h3><div>We show that BHB mitigates cardiac fibrosis in DCM rats by promoting M2 macrophage polarization. BHB may be a useful therapeutic approach for DCM treatment.</div></div>","PeriodicalId":11249,"journal":{"name":"Diabetes research and clinical practice","volume":"229 ","pages":"Article 112461"},"PeriodicalIF":7.4000,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Beta-hydroxybutyrate ameliorates cardiac fibrosis in diabetic cardiomyopathy rats via regulating macrophage polarization\",\"authors\":\"Mei He ,&nbsp;Weiguang Luo ,&nbsp;Shuwei Ning ,&nbsp;Yuexin Yu ,&nbsp;Bin Yang ,&nbsp;Zhikun Guo\",\"doi\":\"10.1016/j.diabres.2025.112461\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Beta-hydroxybutyrate (BHB) has been demonstrated to enhance cardiac function in patients with diabetic cardiomyopathy (DCM), the underlying mechanism remains unclear.</div></div><div><h3>Methods</h3><div>A DCM rat model was established, BHB was administered via intraperitoneal injection. The therapeutic effects of BHB were assessed based on cardiac function, fasting glucose levels, myocardial fibrosis markers and myocardial macrophage polarization. To elucidate the mechanism of action, co-culture experiments were conducted using cardiac fibroblasts and peritoneal macrophages to evaluate collagen expression in fibroblasts and macrophage polarization under BHB treatment.</div></div><div><h3>Results</h3><div>BHB improved cardiac function in DCM rats, reduced fasting glucose levels, alleviated cardiac fibrosis and modulated macrophage polarization. After BHB treatment, the proportion of M1 macrophages decreased while that of M2 macrophages increased in the myocardium of DCM rats. Cardiac fibroblasts isolated from neonatal rats, when co-cultured with peritoneal macrophages under high-glucose conditions, exhibited altered macrophage polarization and collagen expression. High-glucose conditions promoted an increase in M1 macrophages and a decrease in M2 macrophages. BHB treatment reversed this trend by reducing M1 macrophages and promoting M2 macrophage polarization.</div></div><div><h3>Conclusions</h3><div>We show that BHB mitigates cardiac fibrosis in DCM rats by promoting M2 macrophage polarization. BHB may be a useful therapeutic approach for DCM treatment.</div></div>\",\"PeriodicalId\":11249,\"journal\":{\"name\":\"Diabetes research and clinical practice\",\"volume\":\"229 \",\"pages\":\"Article 112461\"},\"PeriodicalIF\":7.4000,\"publicationDate\":\"2025-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetes research and clinical practice\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0168822725004759\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes research and clinical practice","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0168822725004759","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

目的:β -羟基丁酸酯(BHB)已被证实可改善糖尿病心肌病(DCM)患者的心功能,但其潜在机制尚不清楚。方法:建立DCM大鼠模型,经腹腔注射给药。根据心功能、空腹血糖水平、心肌纤维化指标和心肌巨噬细胞极化评价BHB的治疗效果。为阐明其作用机制,采用心脏成纤维细胞和腹腔巨噬细胞共培养实验,评价BHB作用下成纤维细胞胶原表达和巨噬细胞极化情况。结果:BHB改善DCM大鼠心功能,降低空腹血糖水平,减轻心肌纤维化,调节巨噬细胞极化。经BHB处理后,DCM大鼠心肌中M1巨噬细胞比例降低,M2巨噬细胞比例升高。从新生大鼠分离的心脏成纤维细胞,当与腹腔巨噬细胞在高糖条件下共培养时,巨噬细胞极化和胶原表达发生改变。高糖条件促进M1巨噬细胞增加和M2巨噬细胞减少。BHB治疗通过减少M1巨噬细胞和促进M2巨噬细胞极化逆转了这一趋势。结论:我们发现BHB通过促进M2巨噬细胞极化来减轻DCM大鼠的心脏纤维化。BHB可能是治疗DCM的有效方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Beta-hydroxybutyrate ameliorates cardiac fibrosis in diabetic cardiomyopathy rats via regulating macrophage polarization

Objective

Beta-hydroxybutyrate (BHB) has been demonstrated to enhance cardiac function in patients with diabetic cardiomyopathy (DCM), the underlying mechanism remains unclear.

Methods

A DCM rat model was established, BHB was administered via intraperitoneal injection. The therapeutic effects of BHB were assessed based on cardiac function, fasting glucose levels, myocardial fibrosis markers and myocardial macrophage polarization. To elucidate the mechanism of action, co-culture experiments were conducted using cardiac fibroblasts and peritoneal macrophages to evaluate collagen expression in fibroblasts and macrophage polarization under BHB treatment.

Results

BHB improved cardiac function in DCM rats, reduced fasting glucose levels, alleviated cardiac fibrosis and modulated macrophage polarization. After BHB treatment, the proportion of M1 macrophages decreased while that of M2 macrophages increased in the myocardium of DCM rats. Cardiac fibroblasts isolated from neonatal rats, when co-cultured with peritoneal macrophages under high-glucose conditions, exhibited altered macrophage polarization and collagen expression. High-glucose conditions promoted an increase in M1 macrophages and a decrease in M2 macrophages. BHB treatment reversed this trend by reducing M1 macrophages and promoting M2 macrophage polarization.

Conclusions

We show that BHB mitigates cardiac fibrosis in DCM rats by promoting M2 macrophage polarization. BHB may be a useful therapeutic approach for DCM treatment.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Diabetes research and clinical practice
Diabetes research and clinical practice 医学-内分泌学与代谢
CiteScore
10.30
自引率
3.90%
发文量
862
审稿时长
32 days
期刊介绍: Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信