肉桂酸减轻缺氧/复氧诱导的大鼠心肌细胞系损伤

doi:10.16352/j.issn.1001-6325.2026.04.0540

摘要/Abstract

摘要： 目的探讨肉桂酸改善缺氧/复氧(A/R)诱导心肌细胞损伤的作用机制。方法将H9c2细胞分组为对照组、A/R组、肉桂酸低和高剂量组、HIF-1α激活剂(DMOG)组、肉桂酸高剂量+HIF-1α抑制剂(IDF-11774)组。CCK-8法检测细胞活力;ELISA检测H9c2细胞上清中乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)活性;透射电镜观察H9c2细胞线粒体超微结构;2',7'-二氯二氢荧光素二乙酸酯(DCFH-DA)荧光探针检测H9c2细胞中活性氧(ROS)荧光强度;试剂盒检测H9c2细胞中丙二醛(MDA)、超氧化物歧化酶(SOD)活性;FerroOrange荧光探针检测H9c2细胞中亚铁(Fe²⁺)荧光强度;Western blot检测H9c2细胞中HIF-1α、SLC7A11、GPX4蛋白。结果与对照组比较,A/R组H9c2细胞中线粒体结构萎缩,嵴破坏严重,部分外膜破裂,H9c2细胞活力、SOD活性及HIF-1α、SLC7A11、GPX4蛋白降低,细胞上清中LDH、CK-MB活性、细胞中ROS荧光强度、MDA水平及Fe²⁺荧光强度升高(P＜0.05);与A/R组比较,肉桂酸低和高剂量组、DMOG组H9c2细胞线粒体结构破坏程度减轻,H9c2细胞活力、SOD活性及HIF-1α、SLC7A11、GPX4蛋白升高,细胞上清中LDH、CK-MB活性、细胞中ROS荧光强度、MDA水平及Fe²⁺荧光强度降低(P＜0.05);IDF-11774减弱了高剂量肉桂酸对A/R诱导的H9c2细胞铁死亡的抑制作用以及对细胞损伤的改善作用。结论肉桂酸可能通过激活HIF-1α/SLC7A11/GPX4通路抑制A/R诱导的H9c2细胞铁死亡,减轻细胞损伤。

关键词: 肉桂酸, 缺氧/复氧, 心肌细胞, 铁死亡

Abstract: Objective To explore the mechanism of cinnamic acid (CA) in improving anoxia/reoxygenation (A/R)-induced myocardial cell injury. Methods H9c2 cells were assigned into control group, A/R group, low-dose and high-dose groups of cinnamic acid, HIF-1α activator (DMOG) group, and high-dose cinnamic acid+HIF-1α inhibitor (IDF-11774) group. Cell viability was assessed using the CCK-8 assay. Levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the supernatant were measured by ELISA. Mitochondrial ultrastructure was observed via transmission electron microscopy. Intracellular reactive oxygen species (ROS) and ferrous iron (Fe²⁺) levels were detected using 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) and FerroOrange fluorescent probes, respectively. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were determined using commercial kits. Protein expression of HIF-1α, SLC7A11, and GPX4 was analyzed by Western blot. Results Compared with the control group, the A/R group exhibited mitochondrial atrophy, severe cristae disruption, and partial outer membrane rupture. Additionally, cell viability and SOD activity, along with HIF-1α, SLC7A11, and GPX4 protein levels, were significantly decreased, whereas LDH and CK-MB release, ROS production, MDA levels, and Fe²⁺ accumulation were significantly increased (P＜0.05). Compared with the A/R group, the low and high-dose cinnamic acid groups, and DMOG group showed reduced mitochondrial structural injury in H9c2 cells, raised cell viability, SOD activity, HIF-1α, SLC7A11, and GPX4 proteins, and decreased cell supernatant LDH, CK-MB levels, cell ROS fluorescence intensity, MDA and Fe²⁺ fluorescence intensity (P＜0.05). IDF-11774 attenuated the inhibitory effect of high-dose cinnamic acid on A/R induced ferroptosis in H9c2 cells and its improvement effect on cell injury. Conclusions Cinnamic acid alleviates A/R-induced cardiomyocyte injury by inhibiting ferroptosis, likely through activation of the HIF-1α/SLC7A11/GPX4 signaling pathway.

Key words: cinnamic acid, anoxia/reoxygenation, myocardial cells, ferroptosis

中图分类号:

R285.5

韩丽婷, 王琰, 陈星, 马佳, 刘洋. 肉桂酸减轻缺氧/复氧诱导的大鼠心肌细胞系损伤[J]. 基础医学与临床, 2026, 46(4): 540-546.

HAN Liting, WANG Yan, CHEN Xing, MA Jia, LIU Yang. Cinnamic acid alleviates anoxia/reoxygenation-induced injury of rat myocardial cell line[J]. Basic & Clinical Medicine, 2026, 46(4): 540-546.

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