Electroacupuncture improves cardiac function in hyperlipidemic rats by enhancing efferocytosis in myocardial macrophages via the PPARγ-LXRα-MerTK pathway

IF 3.3 3区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Journal of Traditional and Complementary Medicine Pub Date : 2024-10-30 DOI:10.1016/j.jtcme.2024.10.003

Yong-Li Han , Shu-Wen Jin , Xiao-Li Pan , Hong-Xing Zhang

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Abstract

Background and aim

Electroacupuncture (EA) is an effective treatment for hyperlipidemia because it decreases the protein expression of peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptor alpha (LXRα). Lowering blood lipids can reverse cardiac insufficiency, but the underlying mechanisms remain unclear. We aimed to explore whether EA reduces blood lipid levels and restores cardiac function in hyperlipidemic rats and to elucidate the underlying mechanism involved.

Procedures

A hyperlipidemic rat model was established by providing the animals with a high-fat diet (HFD). Animals were divided into normal control diet (NC), HFD, PPARγ siRNA, EA, and EA + PPARγ siRNA groups. H&E staining was used to observe the histopathology of the heart and liver. Transmission electron microscopy and oil red O staining were used to detect the distribution of myocardial lipid droplets and the efferocytosis of macrophages. Double immunofluorescence was used to detect the expression of ATP binding cassette transport A1 (ABCA1), ATP binding cassette transport G1 (ABCG1), PPARγ, LXR, and MER proto-oncogene tyrosine kinase (MerTK) in cardiac macrophages. The MerTK−/− rats and littermate wild-type rats were divided into NC, HFD, and EA groups. The efferocytosis rate of myocardial macrophages in different groups was detected using TUNEL and Annexin V-FITC/PI double staining.

Results and conclusion

EA had positive effects on the blood lipid profile, cardiac function, and heart and liver weights; reduced fat deposition in cardiomyocytes and hepatocytes; promoted reverse cholesterol transport; and enhanced macrophage efferocytosis in HFD-fed rats. This effect was blocked by PPARγ siRNA. The protein expression of the PPARγ-LXRα-MerTK pathway was also increased by EA treatment. However, under MerTK−/− conditions, the beneficial effects of EA on efferocytosis in myocardial macrophages were blocked. EA reversed ectopic lipid deposition in the liver and heart, increased efferocytosis in myocardial macrophages, improved hyperlipidemia, and ameliorated cardiac dysfunction in HFD-fed rats through the PPARγ-LXRα-MerTK pathway.

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电针通过PPARγ-LXRα-MerTK通路增强心肌巨噬细胞的胞浆功能，改善高脂血症大鼠心功能

背景和目的电针（EA）可降低过氧化物酶体增殖物激活受体γ (PPARγ)和肝脏X受体α (LXRα)的蛋白表达，是治疗高脂血症的有效方法。降低血脂可以逆转心功能不全，但其潜在机制尚不清楚。我们的目的是探讨EA是否能降低高脂血症大鼠的血脂水平和恢复心脏功能，并阐明其潜在的机制。方法采用高脂饮食法建立高脂血症大鼠模型。将动物分为正常对照组（NC）、HFD组、PPARγ siRNA组、EA组和EA + PPARγ siRNA组。H&；E染色观察大鼠心、肝组织病理学变化。透射电镜及油红O染色检测心肌脂滴分布及巨噬细胞的efferocylosis。采用双免疫荧光法检测心肌巨噬细胞中ATP结合盒转运A1 （ABCA1）、ATP结合盒转运G1 （ABCG1）、PPARγ、LXR、MER原癌基因酪氨酸激酶（MerTK）的表达。将MerTK - / -大鼠和同窝野生型大鼠分为NC组、HFD组和EA组。TUNEL和Annexin V-FITC/PI双染色检测各组心肌巨噬细胞的efferocytic率。结果与结论ea对血脂、心功能、心肝质量均有积极影响；心肌细胞和肝细胞脂肪沉积减少；促进逆向胆固醇运输；并增强了hfd喂养大鼠的巨噬细胞efferocytosis。这种作用被PPARγ siRNA阻断。EA处理后PPARγ-LXRα-MerTK通路的蛋白表达也增加。然而，在MerTK−/−条件下，EA对心肌巨噬细胞efferocytosis的有益作用被阻断。EA通过PPARγ-LXRα-MerTK通路逆转hfd喂养大鼠肝脏和心脏的异位脂质沉积，增加心肌巨噬细胞的efferocytosis，改善高脂血症，改善心功能障碍。

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来源期刊

Journal of Traditional and Complementary Medicine Medicine-Complementary and Alternative Medicine

CiteScore

9.30

自引率

6.70%

发文量

审稿时长

66 days

期刊介绍： eJTCM is committed to publish research providing the biological and clinical grounds for using Traditional and Complementary Medical treatments as well as studies that demonstrate the pathophysiological and molecular/biochemical bases supporting the effectiveness of such treatments. Review articles are by invitation only. eJTCM is receiving an increasing amount of submission, and we need to adopt more stringent criteria to select the articles that can be considered for peer review. Note that eJTCM is striving to increase the quality and medical relevance of the publications.