Wang Hai-Tao, Yang Wen-Qian, Liu Yu-Qian
Institute of Sports and Health Promotion, Lingnan Normal University, Zhanjiang 524048.
School of Physical Education and Sports Science,Lingnan Normal University, Zhanjiang 524048.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Mar;38(2):143-148. doi: 10.12047/j.cjap.6234.2022.026.
To illuminate the protective effects of pathway in inhibiting ferroptosis by glutathione peroxidase 4 (GPX4) activated by nuclear factor erythroid 2-related factor 2 (Nrf2) during aerobic exercise against myocardial injury in high-fat diet mice. Forty 5-week-old SPF C57BL/6 male mice were randomly divided into the control group (NC), the exercise group (NE), the high fat group (HC) and the high fat diet with exercise group (HE, began at the same time). There were 10 mice in each group. The mice in the high fat diet group were fed with 60% Kcal SPF high fat model diet. Aerobic exercise was performed using increasing load platform exercise, 5 days /week, 60 min/d, the speed started from 13m/min, and increased by 1m/min every two weeks. Myocardium and blood samples were collected after 14 weeks. Structural changes of myocardial tissues were observed by HE staining. Western blot was used to detect the expressions of Nrf2/GPX4/Ferroptosis related proteins in myocardium. Myocardial peroxide concentration and antioxidant enzyme activity were measured by spectrophotometry. Myocardial mitochondrial 8-hydroxy-2 deoxyguanosine (8-OHdG) and serum insulin were measured by ELISA. Compared with the NC group, there was more lipid accumulation in the myocardial fiber space in the HC group, and the levels of FBG and FINS were increased significantly, while ISI was decreased significantly (＜0.01). Compared with the HC group, the lipid concentration was decreased in the HE group, and the activities of total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD) and glutathione (GSH) were increased significantly, while the levels of mitochondrial 8-OHdG and myocardial iron content were decreased (＜0.01). The expression levels of Ferroportin1 (FPN1), ferritin heavy chain 1 (FTH1), GPX4, glucose transporter (GLUT1) and Nrf2 in the HE group were significantly higher than those in the HC group (＜0.01). The expression of GPX4 was enhanced by more Nrf2 transposition into the nuclear during aerobic exercise, which inhibited the occurrence of myocardial ferroptosis. The activities of antioxidant enzymes were promoted and inhibited the peroxidation damage of myocardial mitochondria.
为阐明在高脂饮食小鼠有氧运动过程中，由核因子红细胞2相关因子2（Nrf2）激活的谷胱甘肽过氧化物酶4（GPX4）通过该通路抑制铁死亡对心肌损伤的保护作用。将40只5周龄的SPF级C57BL/6雄性小鼠随机分为对照组（NC）、运动组（NE）、高脂组（HC）和高脂饮食运动组（HE，同时开始）。每组10只小鼠。高脂饮食组小鼠喂食60%千卡的SPF级高脂模型饮食。采用递增负荷平台运动进行有氧运动，每周5天，每天60分钟，速度从13米/分钟开始，每两周增加1米/分钟。14周后采集心肌和血液样本。通过苏木精-伊红（HE）染色观察心肌组织的结构变化。采用蛋白质免疫印迹法检测心肌中Nrf2/GPX4/铁死亡相关蛋白的表达。用分光光度法测定心肌过氧化物浓度和抗氧化酶活性。用酶联免疫吸附测定法（ELISA）检测心肌线粒体8-羟基-2'-脱氧鸟苷（8-OHdG）和血清胰岛素。与NC组相比，HC组心肌纤维间隙脂质蓄积更多，空腹血糖（FBG）和空腹胰岛素（FINS）水平显著升高，而胰岛素敏感指数（ISI）显著降低（＜0.01）。与HC组相比，HE组脂质浓度降低，总抗氧化能力（T-AOC）、总超氧化物歧化酶（T-SOD）和谷胱甘肽（GSH）活性显著升高，而线粒体8-OHdG水平和心肌铁含量降低（＜0.01）。HE组铁转运蛋白1（FPN1）、铁蛋白重链1（FTH1）、GPX4、葡萄糖转运蛋白（GLUT1）和Nrf2的表达水平显著高于HC组（＜0.01）。有氧运动期间更多Nrf2转位入核增强了GPX4的表达，抑制了心肌铁死亡的发生。促进了抗氧化酶活性，抑制了心肌线粒体的过氧化损伤。
