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  

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 秦珊珊 熊诗强 杨佳丽 何建 岳田 侯君 Danzengdunzhu;GAO Han;QIN Shanshan;XIONG Shiqiang;YANG Jiali;HE Jian;YUE Tian;HOU Jun(Medical College,Tibet University,Lhasa 850000,Tibet,China;Department of Cardiology,The Third People’s Hospital of Chengdu,Chengdu 610031,Sichuan,China)

机构地区：[1]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

出　　处：《心血管病学进展》2025年第4期371-377,共7页Advances in Cardiovascular Diseases

基　　金：国家自然科学基金(81900339);西藏自治区自然科学基金重点项目(XZ202201ZR0036G);成都市医学科研项目(2022038);成都市第三人民医院1类孵化项目(CSY-YN-01-2023-003)。

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/低氧环境下的右心室结构与功能、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,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,研究PLIN5通过调控脂肪酸代谢对线粒体的保护作用。结果低氧肺动脉高压存在右心室结构改变与功能下降,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肪酸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肪酸代谢异常引起的心肌细胞损伤。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 fatty acid metabolism by regulating fatty acid metabolism.Conclusion PLIN5 protects hypoxic pulmonary hypertension cardiomyocytes from mitochondrial damage induced by abnormal fatty acid metabolism by regulating fatty acid metabolism of fatty acid synthesis and oxidation.

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 

分 类 号：R541.6[医药卫生—心血管疾病]