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木犀草素通过NR4A2/p53调控抑制细胞凋亡和促进自噬,改善代谢综合征诱导的大鼠心脏损伤模型。

Luteolin ameliorates rat model of metabolic syndrome-induced cardiac injury by apoptosis suppression and autophagy promotion via NR4A2/p53 regulation.

作者信息

Dai Xiyan, Liang Bo, Sun Yaolin

机构信息

Department of Comprehensive, Maoming People's Hospital, Maoming, 525000, China.

Department of MRI, Maoming People's Hospital, Maoming, 525000, China.

出版信息

BMC Complement Med Ther. 2025 Jan 20;25(1):14. doi: 10.1186/s12906-025-04749-6.

DOI:10.1186/s12906-025-04749-6
PMID:39833877
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11744851/
Abstract

BACKGROUND

Reduced cardiac autophagy, inflammation, and apoptosis contribute to cardiovascular complications caused by metabolic syndrome (MetS). It is documented that the nuclear receptor 4A2 (NR4A2) could modulate autophagy and apoptosis in cardiac complications. The aim of this investigation was to assess the therapeutic potential of luteolin, with documented beneficial properties, against MetS-associated cardiac injury.

METHODS

Forty male albino Wistar rats were divided into 5 groups randomly as controls, MetS, and MetS animals treated with luteolin (25, 50, 100 mg/kg ip). The animal's weight, blood pressure, lipid profile, tolerance to glucose and insulin, and cardiac histopathology were evaluated. Moreover, troponin T, creatine kinase-myocardial band (CK-MB), inflammatory profile (IL-6, IL-1β, TNF-α), transforming growth factor-β1 (TGF-β1), oxidative stress, and matrix metalloproteinase-9 (MMP-9) were analyzed to determine the cardiac state. Cardiac NR4A2 and p53, as well as apoptotic (B-cell leukemia/lymphoma 2 [BCL-2], Caspase [CASP]-3, and CASP-9) and autophagic mediators (Sequestosome-1/p62, Microtubule-associated protein 1 A/1B-light chain 3 [LC3], and Beclin-1) were measured by RT-qPCR and ELISA.

RESULTS

Luteolin remarkably restored MetS-induced biochemical derangements and related cardiac injury via the suppression of apoptosis, inflammation, and stress but promotion of autophagy (p-value < 0.001).

CONCLUSION

Current findings revealed the promising therapeutical properties of luteolin against MetS-associated cardiovascular risks.

摘要

背景

心脏自噬、炎症和凋亡减少会导致代谢综合征(MetS)引起的心血管并发症。有文献记载,核受体4A2(NR4A2)可调节心脏并发症中的自噬和凋亡。本研究的目的是评估具有已证实有益特性的木犀草素对MetS相关心脏损伤的治疗潜力。

方法

将40只雄性白化Wistar大鼠随机分为5组,即对照组、MetS组以及用木犀草素(25、50、100mg/kg腹腔注射)治疗的MetS组动物。评估动物的体重、血压、血脂谱、葡萄糖和胰岛素耐受性以及心脏组织病理学。此外,分析肌钙蛋白T、肌酸激酶心肌带(CK-MB)、炎症指标(IL-6、IL-1β、TNF-α)、转化生长因子-β1(TGF-β1)、氧化应激和基质金属蛋白酶-9(MMP-9)以确定心脏状态。通过RT-qPCR和ELISA检测心脏NR4A2和p53以及凋亡介质(B细胞淋巴瘤/白血病2 [BCL-2]、半胱天冬酶[CASP]-3和CASP-9)和自噬介质(聚集体蛋白-1/p62、微管相关蛋白1A/1B轻链3 [LC3]和Beclin-1)。

结果

木犀草素通过抑制凋亡、炎症和应激但促进自噬,显著恢复了MetS诱导的生化紊乱和相关心脏损伤(p值<0.001)。

结论

目前的研究结果揭示了木犀草素对MetS相关心血管风险具有有前景的治疗特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/6347114d2e5b/12906_2025_4749_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/39acb1879179/12906_2025_4749_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/7771323107a1/12906_2025_4749_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/44927e4f85e9/12906_2025_4749_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/3b3a5508d43e/12906_2025_4749_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/a7ccc440d50e/12906_2025_4749_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/4cbe16ba5072/12906_2025_4749_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/45c5dffbb5dd/12906_2025_4749_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/e5112d07ecd6/12906_2025_4749_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/6347114d2e5b/12906_2025_4749_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/39acb1879179/12906_2025_4749_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/7771323107a1/12906_2025_4749_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/44927e4f85e9/12906_2025_4749_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/3b3a5508d43e/12906_2025_4749_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/a7ccc440d50e/12906_2025_4749_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/4cbe16ba5072/12906_2025_4749_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/45c5dffbb5dd/12906_2025_4749_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/e5112d07ecd6/12906_2025_4749_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cf0/11744851/6347114d2e5b/12906_2025_4749_Fig9_HTML.jpg

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