Department of Cardiology, Guangzhou Hospital of Integrated Chinese and Western Medicine, Guangzhou, China.
Dis Markers. 2021 Nov 23;2021:9628521. doi: 10.1155/2021/9628521. eCollection 2021.
Myocardial ischemia-reperfusion injury (MIRI) is the leading cause of death in patients with cardiovascular disease. The purpose of this study is to investigate the effect and mechanism of forkhead box C2 (FOXC2) on MIRI in rats.
We made ischemia-reperfusion (I/R) models for rats by performing I/R surgery. After 3 hours, 3 days, and 7 days of reperfusion, we detected the structure and function of rat myocardium by 2, 3, 5-triphenyl tetrazolium chloride staining, echocardiography, lactate dehydrogenase kit, and haematoxylin-eosin staining. The change of FOXC2 expression in myocardial tissue was also detected. Then, we increased the expression of FOXC2 in rats by adenovirus transfection to clarify the effect of FOXC2 on changes of oxidative stress and inflammation of rat myocardium. In addition, we detected the effect of FOXC2 overexpression plasmid on the function of H9c2 cells . The expression changes of Nrf2/HO-1 in myocardial cells were also detected to clarify the mechanism of action of FOXC2.
The expression of FOXC2 in I/R rats was significantly lower than that in the sham group. After overexpressing FOXC2 in I/R rats, we found that the expression of SOD1/2 of rat myocardium and inflammatory factors in the serum were significantly reduced. Overexpression of FOXC2 also increased the viability and antioxidant capacity of H9c2 cells. In addition, FOXC2 was found to increase the activity of the Nrf2/HO-1 signaling pathway in myocardial cells, and the inhibition of Nrf2/HO-1 signaling pathway attenuated the protective effect of FOXC2 on myocardial cells.
MIRI in rats was accompanied by low expression of FOXC2 in myocardial tissue. Overexpression of FOXC2 reduces the level of inflammation and oxidative stress in myocardial tissue by promoting the Nrf2/HO-1 signaling pathway, thereby alleviating MIRI.
心肌缺血再灌注损伤（MIRI）是心血管疾病患者死亡的主要原因。本研究旨在探讨叉头框 C2（FOXC2）对大鼠 MIRI 的作用及其机制。
通过进行缺血再灌注（I/R）手术，我们为大鼠制作了 I/R 模型。在再灌注 3 小时、3 天和 7 天后，我们通过 2,3,5-三苯基四氮唑氯化物染色、超声心动图、乳酸脱氢酶试剂盒和苏木精-伊红染色检测大鼠心肌的结构和功能。还检测了心肌组织中 FOXC2 表达的变化。然后，我们通过腺病毒转染增加大鼠 FOXC2 的表达，以阐明 FOXC2 对大鼠心肌氧化应激和炎症变化的影响。此外，我们还检测了 FOXC2 过表达质粒对 H9c2 细胞功能的影响。还检测了心肌细胞中 Nrf2/HO-1 的表达变化，以阐明 FOXC2 的作用机制。
I/R 大鼠中 FOXC2 的表达明显低于假手术组。在 I/R 大鼠中过表达 FOXC2 后，我们发现大鼠心肌 SOD1/2 的表达和血清中炎症因子的表达明显降低。FOXC2 的过表达还增加了 H9c2 细胞的活力和抗氧化能力。此外，FOXC2 被发现增加了心肌细胞中 Nrf2/HO-1 信号通路的活性，而 Nrf2/HO-1 信号通路的抑制减弱了 FOXC2 对心肌细胞的保护作用。
大鼠的 MIRI 伴有心肌组织中 FOXC2 的低表达。FOXC2 的过表达通过促进 Nrf2/HO-1 信号通路降低心肌组织中的炎症和氧化应激水平，从而缓解 MIRI。
