[1]旦增顿珠 高寒 秦珊珊 熊诗强 杨佳丽 何建 岳田 侯君.PLIN5通过调节脂肪酸代谢改善肺动脉高压心室功能的作用机制研究[J].心血管病学进展,2025,(4):371.[doi:10.16806/j.cnki.issn.1004-3934.2025.04.018]
 DANZENG Dunzhu,GAO Han,QIN Shanshan,et al.Mechanism of Action of PLIN5 in Improving Ventricular Function in Pulmonary Arterial Hypertension by Regulating Fatty Acid Metabolism[J].Advances in Cardiovascular Diseases,2025,(4):371.[doi:10.16806/j.cnki.issn.1004-3934.2025.04.018]
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PLIN5通过调节脂肪酸代谢改善肺动脉高压心室功能的作用机制研究()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2025年4期
页码:
371
栏目:
论著
出版日期:
2025-04-25

文章信息/Info

Title:
Mechanism of Action of PLIN5 in Improving Ventricular Function in Pulmonary Arterial Hypertension by Regulating Fatty Acid Metabolism
作者:
旦增顿珠1 高寒 1 秦珊珊1 熊诗强2 杨佳丽 2 何建 2 岳田 2 侯君 2
西藏大学医学院,西藏 拉萨 850000;2.成都市第三人民医院心内科,四川 成都 610031)
Author(s):
DANZENG Dunzhu1GAO Han1QIN Shanshan1XIONG Shiqiang2YANG Jiali2HE Jian2YUE Tian2HOU Jun2
(1. Medical College,Tibet University,Lhasa 850000,Tibet,China; 2. Department of Cardiology,The Third Peoples Hospital of Chengdu,Chengdu 610031,Sichuan,China)
关键词:
低氧肺动脉高压脂滴包被蛋白5脂肪酸代谢线粒体
Keywords:
Hypoxic pulmonary hypertensionPerilipin 5Fatty acid metabolismMitochondria
DOI:
10.16806/j.cnki.issn.1004-3934.2025.04.018
摘要:
目的 探究脂滴包被蛋白5(PLIN5)在低氧肺动脉高压大鼠脂代谢异常中的作用及潜在的影响过程。 方法 通过低压氧舱构建低氧肺动脉高压大鼠模型,并评估正常/PLIN5敲除 大鼠在正常/低氧环境下右心室结构与功能、血流动力学指标用以评价右心室功能。通过全身脂质代谢积累以及心脏局部脂肪酸代谢产物水平变化评估低氧环境及PLIN5在此过程中对脂肪酸代谢的影响。随后评估了低氧及PLIN5对脂肪酸代谢中关键酶表达及活性的影响,用以探索PLIN5潜在的影响脂肪酸代谢的过程。通过对心肌细胞线粒体的结构与功能进行评价,探究PLIN5通过调控脂肪酸代谢对线粒体保护作用。结果 低氧肺动脉高压存在右心室的结构改变与功能的下降,且PLIN5的缺失加重了右心室结构改变与功能下降。PLIN5在正常环境下会影响大鼠的脂肪酸代谢但尚未致病,对低氧肺动脉高压大鼠,PLIN5显著影响了其脂肪酸代谢,表现为脂肪酸合成受阻及脂肪酸氧化受限。PLIN5通过调控脂肪酸合成酶?激素敏感性脂肪酶的活性来调控脂肪酸的合成与氧化。同时,PLIN5能通过调控脂肪酸代谢保护心肌细胞线粒体免受脂代谢异常引起的线粒体损伤。 结论 PLIN5通过 调节脂肪酸代谢的脂肪酸合成与氧化过程保护低氧肺动脉高压心肌细胞免受脂代谢异常引起的心肌细胞损伤。
Abstract:
Objective To investigate the role and potential influence of Perilipin 5 (PLIN5) in the abnormalities of lipid metabolism in hypoxic pulmonary hypertension rats. Methods The rat models of hypoxic pulmonary hypertension were constructed by means of a hypobaric oxygen chamber ,and right ventricular structure and function and haemodynamic indexes were assessed in normal/PLIN5 knockout mice in a normal/hypoxic environment for evaluating right ventricular function. The effects of hypoxia and PLIN5 on fatty acid metabolism were assessed by systemic lipid metabolism accumulation and changes in local fatty acid metabolite levels in the heart. The effects of hypoxia and PLIN5 on the expression and activity of key enzymes in fatty acid metabolism were subsequently evaluated to explore the potential influence of PLIN5 on fatty acid metabolism. By evaluating the structure and function of cardiomyocyte mitochondria,we explored the protective effect of PLIN5 on mitochondria through the regulation of fatty acid metabolism. Results Hypoxic pulmonary hypertension was associated with structural changes and functional decline of the right ventricle,which were aggravated by PLIN5 deficiency. PLIN5 affects fatty acid metabolism in rats under normal conditions but is not pathogenic. In rats with hypoxic pulmonary hypertension,PLIN5 significantly affects fatty acid metabolism,as evidenced by the blockage of fatty acid synthesis and the limitation of fatty acid oxidation. PLIN5 regulates fatty acid synthesis and oxidation by modulating the activities of fatty acid synthase and hormone-sensitive lipase. Meanwhile,PLIN5 can protect cardiomyocyte mitochondria from mitochondrial damage caused by abnormal lipid metabolism by regulating fatty acid metabolism. Conclusion PLIN5 protects hypoxic pulmonary hypertension cardiomyocytes from mitochondrial damage induced by abnormal lipid metabolism by regulating fatty acid metabolism of fatty acid synthesis and oxidation

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更新日期/Last Update: 2025-05-16